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Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Supplemental Table S7. Primary PK parameters for spartalizumab

Supplementary Data 3 & 4

Purpose:HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988).Patients and Methods:A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1.Results:IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses.Conclusions:IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.

Supplemental Figure S2. Adverse events in crossover group

Supplemental Table S2. Chemotherapy regimens given to patients in the chemotherapy arm

Supplemental Table S5. Adverse events ({greater than or equal to} 15% incidence of all grades events in any of the patient treatment arms)

Supp. Table 1; Supp. Table 2; Supp. Table 3 A,B; Supp. Table 4; Supp. Table 5; Supp. Table 6; Supplementary Data 1; Supplementary Data 2

Supplemental Table S6. Adverse events of special interest (patients treated with spartalizumab)

Purpose:No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC.Patients and Methods:Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice.Results:Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression.Conclusions:Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

Supplemental Figure S3. Best percentage change from baseline in sum of diameters of target lesions for patients treated with spartalizumab (A) and chemotherapy (B)

Supplemental Table S1. Patient disposition

Supplemental Figure S1. CONSORT diagram

e13517 Background: Data on safety of COVID-19 vaccination in malignancy patients, particularly those receiving cancer treatment, is lacking because they are excluded from vaccine trials. We aimed to evaluate vaccine-related adverse events (VRAEs) in actively treated cancer patients. Methods: This prospective, observational study of VRAEs following ChAdOx1-nCoV-19 vaccine among 399 solid malignancy patients on active cancer treatment was conducted in two Thai academic hospitals. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Solicited and unsolicited VRAEs were collected using questionnaires. The primary endpoint was incidence of VRAEs among solid cancer patients, as compared to healthy controls. Results: 399 cancer patients received cancer treatments during the first dose of vaccine (43% chemotherapy, 34% targeted therapy, 8% immunotherapy, 4% hormonal therapy and 11% combination regimen) and 359 patients continuing the treatments during the second dose. Mean age of the cancer patients was significantly higher than the healthy volunteers (59 +/- 13 vs 48 +/- 13 years, P < 0.001). In overall population, incidence of VRAEs was significantly lower in cancer patients than in healthy controls (57% vs 80%, P < 0.001 in overall periods, 63% vs 93%, P < 0.001 after first dose; and 51% vs 66%, P 0.01 after second dose). In age-matched comparison including 76 cancer patients and 75 healthy volunteers, the incidence of VRAEs in cancer patients was significantly lower than healthy controls only after the first dose (82% vs 93%, P 0.03) but not after the second dose (64% vs 67%, P 0.77) and overall periods (74% vs 79%, P 0.32). There was no significant difference in severity of VRAEs between two groups following the first and second dose. In all patients of cancer cohort, the most common VRAEs were pain at injection site (first dose 39%, second dose 30%), fatigue (first dose 38%, second dose 27%) and myalgia (first dose 33%, second dose 23%). The most common grade 3 VRAEs was fatigue (1%) after the first dose and tenderness at injection site (2%) after the second dose. Fever was the only VRAEs led to interrupting the cancer treatment in two cases (0.5%). Among the cancer treatment types, patients who received a chemotherapy-containing regimen had a lower risk of VRAEs than those who received a non-chemotherapy regimen (odd ratio (OR) 0.2, P 0.001 after first dose and OR 0.4, P 0.001 after second dose). Conclusions: In age-matched comparison,the overall incidence of VRAEs in actively treated patients with solid malignancy following ChAdOx1-nCoV-19 vaccine was comparable to healthy controls. Most occurred VRAEs are mild severity and rarely interfered the cancer treatment. These findings assure that Covid-19 vaccination is safe in cancer patients undergoing treatment.

12099 Background: Hypersensitivity reaction (HSR) is a common toxicity in patients receiving repeated oxaliplatin. Oxaliplatin induced HSR could be severe and results in treatment discontinuation. There is no standard recommendation for prevention of oxaliplatin induced HSR. Methods: We conducted a prospective, single center, open-label, randomized controlled trial comparing the standard premedication and 2-hour infusion protocol to the additional antihistamine premedication, intravenous chlorpheniramine, and 3-hour infusion protocol. After three months of chemotherapy, the randomization was done at 5thand 7th cycles of 3-week and 2-week oxaliplatin based regimens, respectively. The primary endpoint was the incidence of HSR. Results: From July 2020 to March 2021, a total of 160 patients underwent randomization (80 patients in both intervention and control groups). After 11 months follow-up, all patients had completed planned treatment cycles. HSRs occurred in 1 (1.3 %) and 10 (12.5%) patients in intervention and control groups, respectively, p = 0.005). There were 6 (7.5%) patients with more than grade 1 HSRs in control groups, but none in intervention group. In the intervention group, one patient with HSR experienced grade 1 erythema and palpitation. There is no report of significant adverse event from anti-histamine premedication or oxaliplatin infusion prolongation. Conclusions: Additional antihistamine premedication and infusion prolongation started in 2nd half of treatment course can significantly reduced HSR incidence in patients receiving oxaliplatin. Clinical trial information: TCTR20210506001.

Summary Background In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging study with similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumab plus paclitaxel for advanced gastric or GEJ adenocarcinoma in Asian, predominantly Chinese, patients. Methods RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine–platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov , NCT02898077 , and has been completed. Findings Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71–4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83–4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613–0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98–9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31–9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771–1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [ Interpretation These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma. Funding Eli Lilly and Company, USA. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Complementary and Alternative Medicine (CAM) is widely used among cancer patients worldwide. This prospective observational study aimed to show the effect of CAM use on chemotherapy delivery in Thai patients.During March 2014 to February 2015, the patients with breast, lung or colorectal cancer receiving first cycle chemotherapy at King Chulalongkorn Memorial Hospital were enrolled. The correlation between CAM using and chemotherapy schedule delay and dose reduction, dose intensity, quality of life and adverse event rates were analyzed.There were 80 (44.20%) patients using CAM among 181 enrolled patients. Seventy six CAM users and 97 non-CAM users receiving 2nd cycle of chemotherapy were included for primary analysis. The chemotherapy schedules were delayed and/or reduced in 40 (52.6%) and 48 (49.5%) in CAM users and non-CAM users, respectively, p =0.681. The mean relative dose intensity (RDI) were 92.4% and 94.1% in CAM and non-CAM users, respectively, p=0.244. However, there were significantly more CAM users receiving chemotherapy less than 90% RDI (34.8% vs 19.8%, p=0.033). As compared to first cycle, at third cycle, the mean QOL score changes were -4.63 (95% CI -2.49-9.27) and -8.02 (-2.36- 9.142) in CAM user and non-CAM user, respectively (p=0.255). There were significantly higher rates of grade 3 or 4 anemia (5.1% vs 0%, p=0.024), and grade 2 malaise (19.0% vs 5.1%, p=0.004) in CAM users.There were similar overall rates of chemotherapy schedule delay and dose reduction between CAM- and non-CAM users. However, there were less CAM-users achieving 90% chemotherapy RDI.

Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression. Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

Purpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988). Patients and Methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1. Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses. Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.

Vitamin D and its cognate intracellular nuclear receptor, namely, vitamin D receptor (VDR), are involved in the regulation of a variety of body metabolic processes, immune function, and oncogenesis. A large number of studies demonstrated the association of low vitamin D levels and variations in five common single nucleotide polymorphisms (SNPs), FokI, BsmI, Tru9I, ApaI, and TaqI, with the risk of several cancers, including colorectal cancers. However, these associations vary among different populations. This case-control study was aimed at analysing whether common single-nucleotide polymorphisms (SNPs) and haplotypes of the vitamin D receptor (VDR) gene contribute to colorectal carcinogenesis in the Thai population. We enrolled 364 Thai participants from King Chulalongkorn Memorial Hospital between 2014 and 2015. Half of the participants underwent colonoscopy and showed a normal colon without polyps (control group) and another half were newly diagnosed patients with colorectal cancer (CRC) by colonoscopy during the index period, were under treatment, or were followed up at the outpatient clinic (case group). Differences in allele and genotype frequencies of five common VDR SNPs, between the case and control groups, were the primary outcome measures. Differences in haplotype frequencies of the five SNPs between the case and control groups were the secondary outcome measures. Among the 364 participants, baseline characteristics were not significantly different between the case and control groups, except for the higher proportion of males in the CRC group. The mean vitamin D level was also not significantly different between the case and control groups (24.6±9.1 vs. 25.3±10.6 ng/mL, p=0.52). None of the five VDR SNPs was associated with CRC development (p>0.05). However, haplotype analysis of these polymorphisms demonstrated that the AGGT haplotype was associated with a decreased risk of CRC (odds ratio 0.24, 95% confidence interval 0.07-0.81, p=0.01). The AGGT haplotype was associated with a lower risk of CRC in the Thai population. This genetic linkage might support the role of vitamin D in colorectal carcinogenesis. However, this finding requires further study within a larger population and a multivariate analysis of other established risk factors.

378 Background: BTC is a rare, heterogenous cancer with poor prognosis. Reports on immunogenic features of BTC suggest checkpoint inhibition may result in antitumor immune responses, and limited clinical activity has been seen with single agents in advanced settings. Durvalumab (PD-L1 inhibitor) + GemCis showed promising antitumor activity in advanced BTC in a phase 2 study. TOPAZ-1 (NCT03875235) is the first global phase 3 study to evaluate first-line immunotherapy + GemCis in advanced BTC. Methods: In this double-blind study, pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomized 1:1 to receive durvalumab (1500 mg every 3 weeks [Q3W]) or placebo + GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by durvalumab (1500 mg Q4W) or placebo until disease progression or unacceptable toxicity. Randomization was stratified by disease status (initially unresectable, recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer). The primary objective was to assess overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff for this interim analysis (11 August 2021), 685 pts were randomized to durvalumab + GemCis (n=341) or placebo + GemCis (n=344; Table). The primary objective was met: durvalumab + GemCis significantly improved OS vs placebo + GemCis (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). PFS was also significantly improved with durvalumab vs placebo (HR, 0.75; 95% CI, 0.64–0.89; p=0.001). ORR was 26.7% with durvalumab and 18.7% with placebo. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 62.7% of pts receiving durvalumab and 64.9% of pts receiving placebo. TRAEs led to discontinuation of any study medication in 8.9% of pts receiving durvalumab and 11.4% of pts receiving placebo. Conclusions: In pts with advanced BTC, durvalumab + GemCis significantly improved OS and PFS vs placebo + GemCis with manageable safety, indicating durvalumab + GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT03875235. [Table: see text]

BackgroundCurrent guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC.MethodsMedical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test.ResultsAmong the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005).ConclusionsTo date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.

Purpose: To compare incidences of hypersensitivity reaction (HSR) between original and generic taxanes including paclitaxel and docetaxel. Methods: We conducted a prospective study enrolling all patients receiving taxanes at King Chulalongkorn Memorial Hospital. Taxanes were infused accordingly to the step-wise rate escalation protocol at this hospital. Active surveillance for HSRs was performed. During the study period, there was only 1 generic brand used for each taxane. We primarily compared the incidences of HSR between original and generic drugs for each taxane. Results: During the period from January 1 to December 31, 2013, a total of 258 consecutive patients receiving taxanes were enrolled; 128 received paclitaxel, i.e. 65 and 63 in the original (Taxol) and generic arms, respectively, and 130 received docetaxel, i.e. 66 and 64 in the original (Taxotere) and generic arms, respectively. Premedication, including antihistamines and dexamethasone, was administered to all patients 30 min before taxane infusion. There were 26 (10.0%) HSR events including 24 grade 2 and 2 grade 3 HSRs. In the paclitaxel group, there were 9 (13.8%) and 7 (11.1%) HSRs in the original and generic arms, respectively (p = 0.791). In the docetaxel group, there were 9 (13.6%) and 1 (1.6%) HSRs in the original and generic arms, respectively (p = 0.017). No life-threatening symptoms or permanent discontinuation of taxanes occurred. Conclusions: In this prospective study, the incidences of HSR were similar with generic and original paclitaxel but significantly different with generic and original docetaxel.

To evaluate the efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for chemotherapy-induced nausea vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy (HEC). In this randomized, double-blind, placebo-controlled, crossover study, we randomly assigned chemotherapy-naive patients receiving HEC to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another treatment arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs. At the first cycle, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (68.7% vs. 25.0%, p

12100 Background: Prevention of chemotherapy-induced nausea and vomiting (CINV) is vital in cancer treatment. Here, we compared the efficacy of netupitant-containing regimen; composed of NEPA, dexamethasone, and olanzapine (NEPAs), which is recommended for preventing CINV from high-emetogenic chemotherapy (HEC) to standard 3-drugs; ondansetron, dexamethasone, olanzapine for preventing CINV from high-dose cisplatin (≥75 mg/m2). Methods: This randomized, double-blind, placebo-control trial randomly assigned untreated patients who were received high-dose cisplatin in a 1:1 ratio to either NEPAs or standard 3-drugs combination regimen. Dose of dexamethasone in NEPAs regimen was modified after preplanned interim safety analysis to increase from 4 to 8 mg per day on days 2-4. The stratification factors were concurrent treatment with radiation and sex. The primary endpoint was the overall complete response (CR) rate defined as no vomiting and no use of rescue antiemetic drugs. The protocol allowed crossover to NEPAs for those who received standard 3-drugs and did not reach CR in the first cycle. We collected outcome in the first 2-cycle of treatment. Results: Between January 2019 and December 2020, hundred patients were randomly assigned to either NEPAs (n = 51) or in-house standard 3-drugs (n = 49). Demographic characteristics were well-balanced in both arms. Total events in both arms were 101 events for NEPAs and 78 events for standard 3-drug. Overall CR rate were 70% and 69% in NEPAs and standard 3-drugs, ( p-value 0.87) respectively. According to emesis phase, CR in acute (0- 24 hrs.) and delay phase (24-120 hrs.) were not different in both arms; 91% vs. 89% and 72% vs. 71% in NEPAs and standard 3-drugs respectively. However, mean nausea VAS score was significantly lower in NEPAs (1.63 vs. 2.02, p-value = 0.001). The ad hoc subgroup analysis shown similar efficacy between before and after protocol amendment of NEPAs regimen in term of delay emesis CR rate; 70.9% vs. 73.9% ( p-value 0.73). Conclusions: The NEPA-containing regimen did not show superiority compare to standard 3-drug in terms of complete response rate for CINV prevention among patients receiving high-dose cisplatin. Furthermore, the dexamethasone dosage of 4 vs. 8 mg per day might not affect the efficacy of delay emesis of the NEPAs regimen. Clinical trial information: TCTR20190508001. [Table: see text]

265 Background: Treatment options for cholangiocarcinoma (CCA) after progression on first-line gemcitabine-based therapy are limited. Fibroblast growth factor receptor 2 ( FGFR2) gene fusions occur in 13–17% of intrahepatic CCA. A single-arm, phase II study (NCT02150967) evaluated infigratinib, an ATP-competitive FGFR1–3-selective oral tyrosine kinase inhibitor, in previously-treated advanced CCA with FGFR fusions/rearrangements. Methods: Adult patients with advanced/metastatic CCA with progression on ≥1 line of systemic therapy received infigratinib 125 mg orally for 21 days of each 28-day cycle until unacceptable toxicity or disease progression. All patients received prophylaxis with the oral phosphate binder sevelamer. Primary endpoint: objective response rate (ORR) by independent central review per RECIST v1.1, with duration of response (DOR). Secondary endpoints: progression-free survival (PFS), disease control rate, overall survival, safety, pharmacokinetics. Approximately 160 patients are planned (120/20/20 patients in Cohorts 1/2/3). This analysis focuses on Cohort 1 (patients with FGFR2 gene fusions or rearrangements without receiving a prior FGFR inhibitor). Results: As of 31 March 2020, 108 patients, including 83 (77%) with FGFR2 fusions, received infigratinib: median age 53 years (range 23–81 years); 54% had received ≥2 prior treatment lines. Median follow-up was 10.6 months (range 1.1–55.9 months). 96 patients (88.9%) discontinued treatment (12 ongoing). Centrally reviewed ORR was 23.1% (95% CI 15.6–32.2) including 1 CR and 24 PRs; median DOR was 5.0 months (range 0.9–19.1 months). Among responders, 8 (32.0%) patients had a DOR of ≥6 months. Median PFS was 7.3 months (95% CI 5.6–7.6 months). Prespecified subgroup analysis: ORR was 34% (17/50) in the second-line setting and 13.8% (8/58) in the third-/later-line setting (3–8 prior treatments). Most common treatment-emergent adverse events (TEAEs, any grade) were hyperphosphatemia (76.9%), eye disorders (67.6%, excluding central serous retinopathy/retinal pigment epithelium detachment [CSR/RPED]), stomatitis (54.6%), and fatigue (39.8%). CSR/RPED occurred in 16.7% of patients (including 1 G3 event; 0 G4). Other common grade 3/4 TEAEs were stomatitis (14.8%; all G3), hyponatremia (13.0%; all G3), and hypophosphatemia (13.0%; 13 G3, 1 G4). Conclusions: Infigratinib is associated with promising anticancer activity and a manageable AE profile in patients with advanced, refractory CCA with an FGFR2 gene fusion or rearrangement. A phase III study of infigratinib versus gemcitabine/cisplatin is ongoing in the front-line setting (NCT03773302). Clinical trial information: NCT02150967.

TPS356 Background: The FGFR family plays an important role in cholangiocarcinoma, with FGFR2 gene fusions detected in about 15% of patients with cholangiocarcinoma. Infigratinib is an FGFR1–3-selective oral tyrosine kinase inhibitor under evaluation in multiple indications including front-line and pre-treated cholangiocarcinoma. CBGJ398X2204 is an ongoing phase II study evaluating the efficacy of single-agent infigratinib in patients with advanced or metastatic cholangiocarcinoma with FGFR genetic alterations who have received prior gemcitabine. Methods: Study CBGJ398X2204 consists of 3 cohorts and patients in all cohorts receive oral infigratinib once daily for 21 days of a 28-day treatment cycle. Treatment will continue until progressive disease, intolerance, withdrawal of consent, or death. Cohort 1 includes patients with FGFR2 gene fusions or translocations. Cohort 2 includes patients with FGFR genetic alterations other than FGFR2 gene fusions (patients in both Cohorts 1 and 2 must not have received any prior FGFR inhibitors). Cohort 3 includes patients with FGFR2 gene fusions who have received prior treatment with a selective FGFR inhibitor other than infigratinib. The primary endpoint is objective response rate (ORR, RECIST v1.1 per central review). Secondary endpoints include overall survival and overall response rate (per investigator). Safety, pharmacokinetics, and exploratory genetic alterations/biomarkers will also be measured. The study was initiated in 2014 and has a planned enrollment of up to 160 patients across all 3 cohorts (120 in Cohort 1, 20 in Cohort 2, and 20 in Cohort 3). Cohort 1 has completed enrollment and findings from this Cohort are the focus of a separate abstract submitted to the meeting. Results are not currently available from Cohorts 2 and 3 (trial in progress). Clinical trial information: NCT02150967.

4591 Background: Cholangiocarcinoma (CCA) is the most common biliary tract malignancy with an estimated incidence of 8,000–10,000 patients/year in the US. Chemotherapy is the most common second-line treatment with reported outcomes in patients with CCA. Response rates of < 10% and median progression-free survival (PFS) times of ~3–4 months have been reported with second-line chemotherapy regimens, including FOLFOX in the ABC-06 trial. Fibroblast growth factor receptor 2 ( FGFR2) fusions occur in 13–17% of CCA and multiple targeted agents are in development for patients with FGFR2 fusions. To date, the outcome of patients with CCA and FGFR2 fusions receiving standard second-line chemotherapy is unknown. Methods: Patients with advanced CCA and FGFR2 fusions after prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase 2 study (NCT02150967) and received the FGFR1–3 selective TKI infigratinib (previously BGJ398) 125 mg orally qd on d1–21, cycles repeated q28 days until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent. A retrospective analysis of a subset of patients who received infigratinib as third- or later-line treatment was performed. Investigator-assessed PFS and best overall response (BOR, per RECIST 1.1) following second-line chemotherapy (pre-infigratinib) and third-line or later-line infigratinib were calculated. Results: Of the 71 patients (44 women; median age 53 years) with FGFR2 fusions enrolled at the time of analysis (datacut 8 August 2018), 37 (52%) were included in this retrospective analysis. Median PFS with standard second-line chemotherapy was 4.63 months (95% CI 2.69–7.16) compared with 6.77 months (95% CI 3.94–7.79) for third- and later-line infigratinib. BOR for second-line chemotherapy was 5.4% (95% CI 0.7–18.2) compared with 21.6% for third- and later-line infigratinib (95% CI 9.8–38.2). Conclusions: Outcomes from second-line chemotherapy in patients with CCA and FGFR2 fusions were similar to those reported in the literature for all patients with CCA regardless of genomic status and remain dismal. Infigratinib administered as third- and later-line treatment resulted in a meaningful PFS and ORR benefit in patients with CCA and FGFR2 fusions. Clinical trial information: NCT02150967 .

e19398 Background: NK-1 receptor antagonist (NK1RA) is a standard anti-emetic agent in chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving high-dose (HD) cisplatin. However, in limited-resource settings, three-drug regimen including olanzapine, ondansetron and dexamethasone is affordable and effective in CINV prevention in these patients. Objectives: To evaluate cost effectiveness of additional NK1RA for CINV prevention in Thai patients receiving HD cisplatin in 3-cycle horizon, societal perspective. Methods: During January to December 2019, 20 patient receiving HD cisplatin were prospectively enrolled to receive standard three-drug regimen at King Chulalongkorn Memorial Hospital. Total medical resource utility, non-medical cost and clinical outcomes were actually collected and used for establishing decisional-tree model and cost-effectiveness analysis. Three arms decisional-tree model was constructed. First, standard strategy, a real-world practice in Thailand, patients received three-drug regimen in all cycles of chemotherapy. Second, NK1RA-rescue strategy, patients received three-drug regimen in the first cycle and additional NK1RA in subsequent cycles if the patients experienced CINV. Third, NK1RA upfront strategy, patients received four drug NK1RA-containing regimen in all cycles. Complete response (CR) rate was assumed to be 92.5% in NK1RA-containing regimen based on clinical trials. The study endpoint is to compare cost and QALYs in term of incremental cost-effectiveness ratio (ICER). Results: CR rates were 90% and 71% in first and second cycle in patients receiving standard regimen. The NK1RA upfront strategy produced greatest QALYs of 0.0351, followed by 0.0328 and 0.0292 in NK1RA-rescue strategy and standard strategy respectively. Mean total costs were 10420.46, 3332.19 and 2841.30 Thai baht (THB) respectively. The ICER of NK1RA-rescue strategy relative to standard strategy was 135,774 THB per QALY and the ICER of NK1RA upfront strategy relative to NK1RA-rescue strategy was 3,096,654 THB per QALY. Therefore, the ICER of NK1RA-rescue strategy but not NK1RA upfront strategy is considered to be cost effective at the willingness-to-pay level of 160,000 THB per QALY. Conclusions: Our findings suggested that the additional NK1RA as a rescue strategy is cost-effective in patients receiving HD cisplatin in Thai health care.

Background HER2/neu is overexpressed in 15-25% of gastric cancer patients and associated with poor prognosis. Treatment with recombinant monoclonal Abs against HER2/neu is effective yet alternatives are needed due to cost and global availability issues. Thus a peptide vaccine (IMU-131) was developed, consisting of 3 fused B-cell epitopes (p467) from the HER2/neu extracellular domain coupled to CRM197 and administered with the adjuvant Montanide. The present study evaluated the optimal/safe vaccine dose leading to immunogenicity and clinical responses. Methods In an open-label multicenter Phase Ib trial (SE-Asia & Eastern Europe), 14 patients with HER2/neu overexpressing ( ++/ +++) gastric adenocarcinoma were recruited to receive 3 injections of IMU-131 (days 0, 14, 35) in combination with chemotherapy (CT). Dose escalation (10, 30 and 50 µg) was performed in 3 cohorts (C) to evaluate safety, immunogenicity and clinical responses. Results No SAEs related to IMU-131 administration were reported. Eleven patients were evaluable for vaccine-specific immune responses and RECIST assessment. Higher HER2-specific IgG levels were observed in C2 (30 µg) vs. C1 (10 µg). 3/5 patients in C2 showed moderate or little increase in HER2-specific Abs, while all C3 patients (50µg) responded with moderate to high Ab levels. According to RECIST, 1 patient showed complete response, 5 partial response and 4 stable disease. Strong correlation between high Ab levels and clinical responses was observed in C3, while this was only moderate in C2. Capacity to inhibit HER2 phosphorylation was tested in patient sera and could be detected in association with strong tumor reduction. Furthermore, patients with good clinical responses, but low Ab titers featured cellular responses with high IFNγ and TNFα/IL-10 ratios. Conclusions The vaccine was well tolerated and safe with Ab responses at the highest dose showing strong correlation with clinical responses. Currently, the 50 µg dose is being evaluated in a Phase II trial with two arms (IMU 131 + CT and CT only). Clinical trial identification NCT02795988. Legal entity responsible for the study Imugene Ltd. Funding Imugene Ltd. Disclosure U. Wiedermann: Research grant / Funding (institution), Officer / Board of Directors, CSO until September 2018: Imugene; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Themis. I. Bulat: Advisory / Consultancy, Research grant / Funding (self), Full / Part-time employment: Arensia Exploratory Medicine . T. Yau: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb. M. Maglakelidzde: Advisory / Consultancy, Research grant / Funding (self), Full / Part-time employment: ARENSIA Exploratory Medicine . T. Ungtrakul: Travel / Accommodation / Expenses: AstraZeneca. C.C. Zielinski: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Officer / Board of Directors, Scientific Advisory Board Member until June 2018: Imugene; Honoraria (self), Advisory / Consultancy: Ariad; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: KGaA; Honoraria (self), Advisory / Consultancy: Fibrogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Athenex. L. Chong: Honoraria (self), Advisory / Consultancy, Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Imugene Ltd. N. Ede: Leadership role, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Imugene Ltd. A. Good: Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Imugene Ltd; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Kazia Therapeutics; Shareholder / Stockholder / Stock options: Living Cell Technologies. All other authors have declared no conflicts of interest.

Purpose: Biliary tract cancer (BTC)is an aggressive disease with a poor prognosis. Most patients are diagnosed at an advanced stage for which curative surgery is not possible and gemcitabine-platinum chemotherapy is the treatment of choice for advanced cases. Several studies had focused on biomarkers to predict response from platinum drugs in lung cancer, but information is limited for BTC. In this study, two single nucleotide polymorphisms (SNPs) in the copper transporter (CTR1) and excision repair cross-complementary group 1 (ERCC1) genes were investigated as predictive biomarkers of objective response to gemcitabine-platinum. Methods: This cohort study aimed to assess any associations of genetic polymorphisms of these proteins active in drug pathway with treatment response in advanced BTC patients. Twenty six patients were enrolled. DNA was extracted from peripheral blood and genetic polymorphisms were assessed by Taqman allelic discrimination assay. Response was evaluated according to RECIST version 1.1. Results: For the CTR1 polymorphism, GT was the most common genotype (61.5%) followed by GG (34.6%), and TT (3.8%). For the ERCC1 polymorphism, only 2 genotypes were found, CC and CT at 57.7% and 42.3%, respectively. Genetic polymorphisms were not found to be singly associated with response. However, when the 2 genetic polymorphisms were combined, GG/CC showed a higher response rate than the others (p=0.018, Fisher’s Exact Test). Conclusion: This is the first study to show an association between CTR1 and ERCC1 polymorphisms and response to gemcitabine-platinum in advanced BTC patients. These polymorphisms might be used as biomarkers to predict response in such cases in the future.

Despite a few global regions with increased incidence, cancers of the biliary tract remain a rare entity. Cholangiocarcinoma has been referred to as an ‘orphan’ cancer, given its relative infrequency in the Western population.

Purpose Cancer patients are a high-risk population for venous thromboembolism (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer patients is not well described in the medical literature. Methods Utilizing a software program the computerized tomographic scan reports of patients at a single cancer center from January 1, 2004 to June 30, 2011 were searched for the term GVT. Patients included in this analysis had a diagnosis of cancer, an isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms referable to the GVT, and at least six months of follow-up information. All subsequent recurrent VTE events were confirmed by imaging studies. Results 196 cancer patients with GVT were identified. The majority of patients in this analysis had metastatic disease (118, 61.2%) as well as active cancer (167, 85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5 months); median time to recurrent VTEs was 5.5 months (range 0–19 months). When considering only patients with without a recent history of gynecologic surgery, VTE recurrence rates were 14.3%. Active cancer was the only risk factor significantly associated with recurrent VTE ( P = 0.047). Conclusions Based upon the patient’s risk factors for VTE, treatment of an incidentally detected GVT in cancer patients with anticoagulation, as per guidelines for other VTE sites, may be indicated in certain high risk subgroups, especially those patients with active cancer who have not had prior pelvic surgery.

Background: HER2/neu is overexpressed in 15-25% of gastric cancer patients and associated with poor prognosis. Alternative treatments to monoclonal antibodies are needed due to cost and global availability issues of mAbs. Thus a B-cell peptide vaccine (IMU-131) was developed, consisting of 3 fused B-cell epitopes (p467) from the HER2/neu extracellular domain coupled to CRM197 applied with the adjuvant Montanide. The current study evaluated the optimal and safe vaccine dose leading to immunogenicity and clinical responses. Material & Methods: In an open-label multicenter Phase Ib trial in SE-Asia and Eastern Europe, 14 patients with HER2/neu overexpressing (++/+++) gastric or gastroesophageal junction adenocarcinoma were recruited to receive 3 injections of IMU-131 (days 0, 14, 35) in combination with chemotherapy (CT) every 21 days. Dose escalation with 10 µg, 30 µg and 50 µg was performed in 3 cohorts. Safety, immunogenicity and clinical responses were evaluated. Results: No SAEs related to administration of IMU-131 were reported. Eleven of 14 patients were evaluable for vaccine-specific immune responses and 10 for tumor growth assessment. Higher p467- and Her-2 specific IgG levels were observed in cohort 2 (30 µg/dose) compared to cohort 1 (10 µg/dose). Two of five patients in cohort 2 showed minimal antibody titers. In contrast, all patients in cohort 3 (50µg/dose) responded to the vaccine with equally high antibody levels. Response rate was an exploratory endpoint and of 10 evaluable patients, 5 patients showed partial response and 4 patients showed stable disease. In cohort 3 the high antibody levels correlated with clinical response, while in cohort 2 only moderate correlations between humoral and clinical responses were observed. In cohort 1 partial response did not correlate with Ab levels, but rather with a high percentage of CD8 T-cells and increased inflammatory cytokine levels (high IFN-γ and TNF-α/IL-10 ratio). Conclusions: The vaccine was well tolerated and safe with antibody responses at the highest dose (50 µg) showing a strong correlation with clinical responses. Thus, a dose of 50 µg was recommended for further evaluation in Phase II, featuring two arms of either IMU 131 plus CT or CT alone. We propose that this vaccine might be of significant medical benefit and further trials are warranted. Citation Format: Ursula Wiedermann, Erika Garner-Spitzer, Yee Chao, Iurie Bulat, Arunee Dechaphunkul, Wichit Arpornwirat, Chaiyut Charoentum, Chia-Jui Yen, Thomas Cheung Yau, Marina Maglakelidze, Suebpong Tanasanvimon, Jedzada Maneechavakajorn, Aumkhae Sookprasert, Li-Yuan Bai, Wen-Chi Chou, Teerapat Ungtrakul, Christoph C. Zielinski, Leslie Chong, Nick Ede, Anthony J Good. A Phase Ib open label multicenter study with a HER2/neu peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy shows safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced cancer of the stomach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT059.

Background: There is currently no standard treatment for patients (pts) with platinum refractory, recurrent metastatic (R/M) NPC. Spartalizumab, a humanized anti-PD-1 IgG4 mAb, blocks interaction with PD-L1 and PD-L2. This is the first randomized phase II study to evaluate efficacy and safety of spartalizumab vs CT in NPC. Methods: This phase II open-label study recruited pts with non-keratinizing locally advanced R/M NPC who progressed on/after platinum-based CT and received up to 2 systemic therapies. Pts were randomized (2:1) to receive spartalizumab or CT, per investigator’s choice. Spartalizumab was dosed 400 mg every 4 weeks intravenously. Pts in CT arm could cross over to receive spartalizumab if progression confirmed by RECIST v1.1, based on independent central review. Primary endpoint was progression free survival (PFS); secondary endpoints were overall response rate (ORR), based on central review by RECIST v1.1, duration of response (DOR), overall survival, safety and pharmacokinetics. Correlation between efficacy and expression of immunologic biomarkers and immune-related genes was also studied. Results: In total, 76 pts in spartalizumab arm and 37 pts in CT arm were randomized (median age 51 years, ECOG performance status 0-2). As of Jan 31, 2018, 18/76 (23.7%) spartalizumab-treated pts, 8/37 (21.6%) CT-treated pts and 4/20 (20.0%) pts in crossover group were ongoing. Discontinuation rates were similar between arms, mainly due to progressive disease in spartalizumab arm (67.0%) and CT arm (68.0%). Median PFS (95% CI) was 1.9 mo (1.8;3.5) in spartalizumab arm vs 6.6 mo (3.7;9.2) in CT arm; primary endpoint was not met, with hazard ratio of 1.53 (95% CI 1.02;2.27). ORR (95% CI) was 18.4% (10.5;29.0) vs 32.4% (18.0;49.8) in spartalizumab vs CT arm, respectively, and 5.0% (0.1;24.9) in crossover group. ORR for pts treated with monotherapy CT was 19.2% (5/26) and for pts treated with CT doublet/triplet was 63.3% (7/11). The Kaplan-Meier estimate of DOR rate at 12 mo in responding spartalizumab-treated pts was 61.0% (95% CI 20.2;85.8). In CT arm, 11/12 pts either progressed or discontinued at 12 mo; at data cut-off, 1 pt remained responding for 3.61 mo. Safety profile of spartalizumab was largely consistent with results obtained from other spartalizumab single-agent studies. Overall, treatment-related grade 3/4 adverse events were reported in 18.4% of spartalizumab-treated pts and 40.5% of CT-treated pts. No treatment-related deaths occurred. RNA sequencing analyses of tumors revealed a correlation between response to spartalizumab and IFN-γ signature, TIM3 and LAG3 gene expression; this correlation was not observed in pts treated with CT. Conclusions: Spartalizumab was well tolerated and despite the study not reaching its primary endpoint, long-lasting tumor responses were observed in a subset of spartalizumab-treated pts with NPC. Biomarker analysis is ongoing. Citation Format: Darren Wan-Teck Lim, Hung-Ming Wang, Shau-Hsuan Li, Roger Ngan, Arunee Dechaphunkul, Li Zhang, Chia Jui Yen, Po Chung Chan, Somvilai Chakrabandhu, Brigette Ma, Suebpong Tanasanvimon, Victor Lee, Pei-Jen Lou, Zujun Li, Alexander Spira, Ammar Sukari, Joël Guigay, Steven McCune, Yongjian Sun, Sebastian Szpakowski, Yao Yao, Xueqiang Fan, Luigi Manenti, Caroline Even. Phase II study of spartalizumab (PDR001) vs chemotherapy (CT) in patients with recurrent/metastatic nasopharyngeal cancer (NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT150.