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Patients with metastatic castration-resistant prostate cancer have few treatment options after novel hormonal therapy (eg, abiraterone or enzalutamide). We aimed to evaluate cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, in combination with the PD-L1 inhibitor atezolizumab in metastatic castration-resistant prostate cancer.COSMIC-021 is an ongoing, multicentre, open-label, phase 1b study with a dose-escalation stage followed by tumour-specific expansion stages. Expansion cohort 6 in metastatic castration-resistant prostate cancer was enrolled at 42 cancer research centres in France, Italy, the Netherlands, Spain, and the USA. Eligible patients were aged 18 years or older and had metastatic castration-resistant prostate cancer with radiographic soft tissue progression following treatment with either enzalutamide or abiraterone, or both; measurable soft tissue disease per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1; and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received oral cabozantinib 40 mg per day and intravenous atezolizumab 1200 mg once every 3 weeks. Study treatment continued until progressive disease or unacceptable toxicity. All enrolled patients were assessed for efficacy and safety. The primary endpoint was objective response rate per RECIST version 1.1 as assessed by the investigator. This study is registered with ClinicalTrials.gov, NCT03170960.Between April 24, 2018, and Aug 31, 2020, 132 patients were enrolled and received at least one dose of study treatment. At data cutoff (Feb 19, 2021), median duration of follow-up was 15·2 months (IQR 9·6-21·7). Objective response rate was 23% (95% CI 17-32; 31 of 132 patients), with three (2%) confirmed complete responses and 28 (21%) confirmed partial responses. 72 (55%) of 132 patients had grade 3-4 treatment-related adverse events, with the most common being pulmonary embolism (11 [8%] patients), diarrhoea (nine [7%]), fatigue (nine [7%]), and hypertension (nine [7%]). There was one grade 5 treatment-related adverse event (dehydration). 74 (56%) of 132 patients had serious adverse events of any causality. 28 (21%) of 132 patients had treatment-related adverse events leading to discontinuation of either study drug.Cabozantinib plus atezolizumab showed promising antitumour activity in patients with metastatic castration-resistant prostate cancer after novel hormonal therapy with an acceptable safety profile, supporting further evaluation of this combination.Exelixis.

Background: HER2-targeted therapies have led to marked improvements in survival for patients with HER2-positive breast cancer. Despite the gains obtained with current HER2-targeted therapies, an unmet medical need remains for patients with HER2-expressing (high or low expression) advanced breast cancer that has progressed after prior treatments. Zanidatamab is a novel HER2-targeted bispecific antibody that has multiple mechanisms of action, including immune clearance of HER2-expressing tumor cells through antibody-dependent cellular phagocytosis. Zanidatamab has been shown to be well-tolerated and has demonstrated antitumor activity, both as monotherapy and in combination with chemotherapy, across HER2-expressing solid tumors in a Phase 1 study. ALX148 is a high affinity CD47-blocking fusion protein with an inactive human immunoglobulin Fc region designed to enhance the activity of anticancer therapies, including antibodies, with minimal added hematologic toxicity. Treatment with zanidatamab in combination with ALX148 has the potential to augment the immune clearance of HER2-expressing cancer cells by blocking the CD47-SIRPa interaction that inhibits phagocytosis of the same cancer cells. In a Phase 1 study, ALX148 demonstrated antitumor activity when combined with trastuzumab in patients whose disease had progressed on prior HER2-targeted therapies. Here, we describe a Phase 1b/2 study to investigate the safety and antitumor activity of a chemotherapy-free combination of zanidatamab plus ALX148 in advanced HER2-expressing cancers, including breast cancer. Methods: ZWI-ZW25-204 is a Phase 1b/2, 2-part, open-label, multicenter study to evaluate the safety and antitumor activity of zanidatamab administered in combination with ALX148 in patients with locally advanced/inoperable and/or metastatic HER2-expressing cancer. Part 1 of this study will evaluate safety and tolerability and will establish the recommended doses (RDs) of zanidatamab plus ALX148. It will include patients with either HER2-positive (defined per ASCO/CAP guidelines) or HER2-low (defined as immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization (ISH) negative) breast cancer. Part 2 will evaluate the antitumor activity of zanidatamab plus ALX148 (at their combination therapy RDs) in 3 expansion cohorts: HER2-positive breast cancer (Cohort 1), HER2-low breast cancer (Cohort 2) and other HER2-overexpressing advanced malignancies (Cohort 3). Other key eligibility criteria include: prior use of approved agents known to confer clinical benefit, disease progression on or after the most recent systemic therapy, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Patients will receive zanidatamab and ALX148, each administered intravenously once every 2 weeks in a 28-day treatment cycle. Response assessments will be performed every 8 weeks. Primary endpoints include safety and tolerability assessments (Part 1) and confirmed objective response rate per RECIST 1.1 (Part 2). Secondary endpoints in Part 2 include disease control rate, clinical benefit rate, duration of response, progression-free survival, overall survival, safety, pharmacokinetics, and immunogenicity assessments. The study is currently open for enrollment in the United States and may enroll up to 93 patients (NCT: 05027139). Citation Format: Sara A. Hurvitz, Jorge Chaves, Adam Brufsky, Alberto J. Montero, Bruno Fang, Kay Yeung, Manish R. Patel, Ritesh Parajuli, Adam Omidpanah, Elaina Gartner, Abraham Fong, Sophia Randolph, Funda Meric-Bernstam. Zanidatamab in combination with ALX148 in advanced human epidermal growth factor receptor 2 (HER2)-expressing cancers, including breast cancer: A phase 1b/2, multicenter, open-label, dose-finding and cohort-expansion study (ZWI-ZW25-204) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-14-01.

720 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA in 2020, with an expected median overall survival (OS) of 3 months in 3rd line. (Manax ASCO GI 2019), with no evidence of disease control in these late stage patients. We hypothesize that effective response against pancreatic cancer requires orchestration of both the innate and adaptive immune system to accomplish immunogenic cell death with survival benefit. Herein we report updated results of the fully enrolled cohort of a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine superagonist ), and allogeneic off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: We report data from a multi-center study, on 83 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. This induction immuno-modulation therapy to induce DAMPs was followed with investigational agents activating the innate and adaptive systems: Aldoxorubicin (150 mg/m2 IV), N-803, an IL-15 superagonist (15 μg/kg SC) and PD-L1 t-haNK (~2 × 109cells/dose IV). Prophylactic G-CSF or EPO was not allowed. All treatments were administered on an outpatient basis. Results: As of submission, median follow-up is 4.9 months. Median age 62, M:F ratio 46:36. ECOG 0-1,97%. 74/83 (89%) reported at least 1 investigational product related AE (TRAE) with 63/83 (76%) reporting at least 1 TRA grade 3 or higher. The most common were anemia 41%, neutropenia 20%, thrombocytopenia 10%, all others =8 weeks. Median OS in 3rd line (N=38) is 6.3 months, Median OS in 4th line or greater (N=40) is 5.0 months. Conclusions: Historical 3 month median OS in 3rd line metastatic pancreatic cancer patients has been exceeded. A doubling of survival in 3rd line is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented. Clinical trial information: NCT03563144 .

In situ observations of snow water equivalent (SWE) from manual snow surveys and automated sensors are made at approximately 1000 sites across Canada in support of water resource planning for flood...

Introduction: Biomarker testing identifies actionable mutations to inform targeted tx for personalized healthcare. This study examined biomarker testing and tx patterns ≤ 90 days (d) after advanced (adv) or metastatic (met) diagnosis (Dx) at the OneOncology (OneOnc) network. Methods: A retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database from selected OneOnc practices included patients (pts) ≥ 18 y, who had Dx between 1/1/18 - 4/30/21 with adv non-small cell lung cancer (aNSCLC), met breast cancer (mBC), met colorectal cancer (mCRC) or adv melanoma (aMel), with ≥ 1 visit ≤ 90 d after adv or met Dx, and who had ≥ 90 d follow-up. Descriptive analyses were conducted. Results: Of the pts who met the inclusion criteria, 91% of 2,391 aNSCLC, 100% of 1,043 mBC, 92% of 1,344 mCRC and 84% of 358 aMel had ≥ 1 biomarker test at any time, where 78% aNSCLC, 82% mBC, 70% mCRC and 67% aMel were tested ≤ 90 d after adv or met Dx. Testing rates varied by biomarker (Table). Across indications, ≥ 70% commercial health insured vs. ≥ 50% Medicaid insured pts were tested. Commercial labs were used in 91% aNSCLC, 86% mBC, 80% mCRC and 93% aMel. Amongst treated pts, 14% of 1,693 aNSCLC, 2% of 725 mBC, 22% of 881 mCRC and 25% of 169 aMel received tx before test results were available. NGS was tested in 69% aNSCLC, 29% mBC, 70% mCRC, and 57% aMel. The median turnaround time (TAT) from adv or met Dx to 1st test result from NGS vs other biomarker tests was 26 vs 13 d in aNSCLC, 14 vs 5 d in mBC, 35 vs 10 d in mCRC and 44 vs 21 d in aMel. Conclusions: The majority of testing occurred ≤ 90 d after adv or met Dx, while 18% - 33% of pts were not tested. The varying testing rates across indications reflect the intended use of biomarker tests to guide 1st line therapies. More than 75% pts treated after testing result available signal community oncologist recognizing the importance of biomarker testing in guiding tx decisions. Improvements in TAT for NGS may reduce the issue of tx decisions made prior to test results. Table. Biomarker testing rate by indication amongst pts tested ≤ 90 d after adv or met Dx aNSCLCn=1,858 mBCn=859 mCRCn=936 aMeln=239 EGFR 89% ALK 87% BRAF 81% 80% 98% KRAS 67% 82% ROS1 86% PD-L1 85% 18% 27% ER 93% PR 93% HER2 92% BRCA 20% PIK3CA 28% MMR/MSI 93% NRAS 77% 49% KIT 50% ER, estrogen receptor; MMR, mismatch repair; MSI, microsatellite instability; PR, progesterone receptor. Citation Format: Esprit Ma, Elaine Yu, Tania Szado, Richard Price, Craig S. Meyer, Anuj Shah, Baiyu Yang, Daniel Vaena, Davey Daniel, Dennis Slater, Harry Staszewski, Bruno Fang, Lasika Seneviratne, Lee Schwartzberg. Biomarker testing and treatment (tx) patterns in a large community oncology network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2267.

9005 Background: C, a multitargeted receptor tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment that may enhance ICI activity. COSMIC-021 (NCT03170960) is a multicenter phase 1b study evaluating C + A in advanced solid tumors. In COSMIC-021, C + A demonstrated encouraging clinical activity in the cohort of pts with aNSCLC previously treated with ICIs (cohort 7 [C7]) (Neal. ASCO 2020. Abstr 9610). Updated outcomes of C + A in expanded C7 and outcomes for C alone in exploratory cohort 20 (C20) are presented. Methods: Pts with stage IV nonsquamous NSCLC without mutations in EGFR, ALK, ROS1, or BRAF V600E who progressed on one prior ICI and ≤2 prior lines of systemic anticancer therapy but no prior VEGFR TKI were eligible. Cohorts were not accrued contemporaneously. Pts received C 40 mg PO QD plus A 1200 mg IV Q3W (C7) or C alone 60 mg PO QD (C20). Primary endpoint was objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Results: A total of 81 and 31 pts received C + A and C, respectively; baseline characteristics were as follows: median age, 67 y, 70 y; male, 57%, 58%; ECOG PS 1, 64%, 71%; liver metastasis, 21%, 23%; refractory to prior ICI (progressive disease [PD] as best response), 32%, 45%; median number of prior systemic therapies, 3 and 3. As of Nov 30, 2021, median follow-up (range) (mo) was 24.7 (10.7, 42.8) and 21.5 (17.3, 27.6) for C + A and C, respectively, with 6 (7%) and 1 (3%) on study treatment. Clinical activity was observed for C + A and C alone (Table). Most common treatment-related adverse events (TRAEs) of any grade for C + A and C, respectively, included diarrhea (40%, 42%), nausea (22%, 45%), decreased appetite (25%, 26%), vomiting (14%, 23%), and fatigue (28%, 19%); grade 3/4 TRAEs occurred in 44% and 52% and one grade 5 TRAE occurred in each cohort (pneumonitis [C + A] and gastric ulcer hemorrhage [C]). Conclusions: C + A and C demonstrated encouraging clinical activity with manageable toxicity in pts with aNSCLC previously treated with ICIs. A phase 3 trial (CONTACT-01; NCT04471428) of C + A vs docetaxel is ongoing in NSCLC previously treated with an ICI and platinum-containing chemotherapy. Clinical trial information: NCT03170960. [Table: see text]

TPS3635 Background: Treatment options for most patients with metastatic colorectal cancer (mCRC) are largely limited to cytotoxic chemotherapy, with little advancement in the last decade. Encouragingly, a small subset of patients deficient in mismatch repair (dMMR/MSI-hi) benefit from checkpoint inhibitors (CPI) whereas those proficient in mismatch repair (pMMR/MSS) do not. The absence of clinical benefit in patients with pMMR/MSS mCRC may relate to a lack of neoantigen-specific T cells and immune infiltration. An individualized neoantigen vaccine that induces CD8 T cells capable of tumor lysis has the potential to expand the number of patients with mCRC who may benefit from immunotherapy. Data from a Phase 1/2 study evaluating neoantigen vaccines in combination with CPIs in patients with previously treated mCRC demonstrated a 44% molecular response (MR) rate (≥50% decrease in ctDNA relative to baseline) in 4/9 patients; this correlated with improvement in OS relative to those without a MR. To further investigate neoantigen vaccines in earlier lines of treatment, a Phase 2/3 study in the1L maintenance setting in mCRC was initiated. Methods: GO-010 is a Phase 2/3, randomized, open-label, multi-center study evaluating the efficacy and safety of 2 neoantigen-containing vectors (GRT-C901-adenoviral vector plus GRT-R902-self-amplifying mRNA vector) as prime/boost in combination with CPIs as an add-on to fluoropyrimidine/bevacizumab (bev) following 1L therapy with FOLFOX/bev in patients with mCRC. During Phase 2, up to 90 patients will be randomized 1:1 to the vaccine or control arm with a primary objective of assessing efficacy by MR. During Phase 3, up to 226 patients will be randomized with a primary objective of assessing PFS per iRECIST in a blinded, independent manner. There are two stages to the study. In the vaccine production stage, while patients receive FOLFOX/bev 1L therapy, neoantigen prediction is performed using a tumor biopsy and Gritstone’s EDGE™ neoantigen prediction model. For patients in the vaccine arm the top 20 predicted neoantigens are included in the vaccine vectors. After completing oxaliplatin, patients will enter the study treatment stage. Patients in the control arm will continue with maintenance therapy whereas patients in the vaccine arm will add the vaccine regimen to maintenance therapy. The vaccine regimen consists of GRT-C901/GRT-R902 as well as SC ipilimumab (30 mg) and IV atezolizumab (1680 mg). Over the first year of treatment, 6 vaccinations will occur. Ipilimumab will be administered SC with the first doses of GRT-C901 and GRT-R902. Atezolizumab will be administered every 4 weeks for up to 2 years. Study assessments include imaging, ctDNA, safety, immunogenicity and exploratory biomarker analysis. Clinical trial information: NCT05141721.

5002 Background: In the phase 3 VISION study, gallium (68Ga) gozetotide (68Ga-PSMA-11) PET/CT imaging was used to determine eligibility for lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617). Given that 177Lu-PSMA-617 targets PSMA, we assessed the association between quantitative PSMA imaging parameters and treatment outcomes. Methods: In VISION, adults with mCRPC with ≥ 1 PSMA-positive (+) and no PSMA-negative lesions meeting the exclusion criteria were enrolled. In this sub-study, the association between imaging data from pre-enrollment 68Ga-PSMA-11 PET/CT scans of pts in the 177Lu-PSMA-617 group and clinical outcomes was assessed. Imaging data meeting quality requirements were analyzed for 548/551 pts. PSMA expression was quantified by 5 PET parameters: PSMA+ lesions by region, mean standardized uptake value (SUVmean), maximum SUV (SUVmax), PSMA+ tumor volume, and tumor load (PSMA+ tumor volume × SUVmean). Parameters were extracted from the whole body and 4 regions. Association between PET parameters and radiographic progression-free survival (rPFS; primary objective), overall survival (OS), objective response rate (ORR), and prostate–specific antigen 50 (PSA50) response was assessed. Results: Most pts (92.7%) had PSMA uptake in bone. In both the whole-body and regional analyses, statistically significant associations of PSMA PET parameters to clinical outcomes were observed (whole-body data shown in Table). Higher whole-body SUVmean was associated with improved clinical outcomes; pts in the highest quartile (SUVmean: rPFS, ≥ 10.2; OS, ≥ 9.9) had a median rPFS and OS of 14.1 and 21.4 months, vs 5.8 and 14.5 months for those in the lowest quartile (< 6.0; < 5.7), respectively. Absence of PSMA+ lesions in bone, liver, and lymph node, and lower PSMA+ tumor load, were indicators of good prognosis. Conclusions: Higher SUVmean is strongly associated with improved outcomes with 177Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of 68Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.[Table: see text]

e18778 Background: Biomarker testing has advanced from single-gene to NGS. This study examined aNSCLC and mBC biomarker testing ≤ 90d of advanced (adv) or metastatic (met) diagnosis (Dx) and treatment (tx) patterns at US practices. Methods: A retrospective observational study used Flatiron Health electronic health-record-derived de-identified database at OneOncology (OO) community and non-OO Flatiron Health nationwide (NAT) sites (̃90% community, ̃10% academic). Patients (Pts) ≥ 18y, with Dx of aNSCLC or mBC from 1/1/18 - 4/30/21, with ≥ 1 visit ≤ 90d after adv/met Dx and ≥ 90d follow-up were evaluated. Descriptive analyses and logistic regression were used. Results: A total of 16,882 pts with aNSCLC (2366 OO; 14,516 NAT), and 6500 pts with mBC (1026 OO; 5474 NAT) were included. Overall testing was high and stable (OO: 85% aNSCLC, 98% mBC; NAT: 84%, 97%) with higher NGS testing at OO (58% aNSCLC; 28% mBC) vs NAT (49%; 16%) (Table), which reflected more pts with aNSCLC tested for all 6 mutations (ALK, BRAF, KRAS, ROS-1, EGFR, PD-L1; 54% OO vs 50% NAT, p0.05); mBC NGS testing increased faster at NAT vs OO (p

95 Background: mCRPC remains an incurable disease with unmet need for improved therapies. PARP inhibition has demonstrated antitumor activity, and preclinical studies suggest synergy between PARP and AKT inhibition. This phase Ib trial (NCT03840200) sought to determine the maximum tolerated dose of PARP inhibitor rucaparib (ruca) with AKT inhibitor ipatasertib (ipat) and explore early safety and efficacy in patients (pts) with mCRPC. Methods: The study had 2 parts: a part 1 dose-escalation phase (cohort [C]1: ipat 300 mg QD + ruca 400 mg BID; C2a: ipat 300 mg QD + ruca 600 mg BID; C2b ipat 400 mg QD + ruca 400 mg BID; C3: ipat 400 mg QD + ruca 600 mg BID) in unselected pts with mCRPC or advanced breast or ovarian cancer, and a Part 2 dose-expansion phase in pts with mCRPC whose previous androgen deprivation therapy failed. The primary safety endpoints were AEs and dose-limiting toxicities, with the goal of identifying a recommended phase II dose (RP2D). The primary efficacy endpoint was prostate-specific antigen (PSA) response (PSA reduction of ≥ 50%) in pts with mCRPC. Secondary efficacy endpoints included ORR per RECIST 1.1, radiographic PFS (rPFS) per Prostate Cancer Working Group 3 and OS in pts with mCRPC. We assessed homologous recombination deficiency (HRD), PIK3CA/ AKT1/ PTEN status and other alterations by next-generation sequencing. Results: Part 1 enrolled 21 pts: 17 with mCRPC, 3 with ovarian cancer and 1 with breast cancer (C1 [n=8], C2a [n=6] and C2b [n=7], C3 [not opened]). Ipat 400 mg QD + ruca 400 mg BID was the selected RP2D. 30 pts enrolled in Part 2, so 37 pts with mCRPC (C2b + Part 2) received the RP2D (median follow-up 93 days). All grade AEs occurred in 37 pts (100%), serious AEs in 8 pts (22%) and AEs leading to treatment modification in 26 pts (70%). The most frequent AEs (all grade and grade 3, respectively) were diarrhea (35 [95%] and 2 [5%]); asthenia (24 [65%] and 4 [11%]); and nausea (24 [65%] and 2 [5%]). There was 1 grade 4 AE (anemia) and no grade 5 AEs. See the table for efficacy data. In biomarker subgroups, the PSA response rate was 50% (3/6) in pts with HRD tumors vs 25% (4/16) in pts with HR-proficient tumors, and 14% (1/7) vs 40% (6/15) in pts with PIK3CA/ AKT1/ PTEN–altered or intact tumors, respectively. Conclusions: The combination of ipat and ruca was well tolerated but did not show clinically relevant antitumor activity in pts with mCRPC, including in predefined biomarker subpopulations. Clinical trial information: NCT03840200. [Table: see text]

2514Background: ONC201 is an orally active, first-in-class small molecule activator of the integrated stress response that selectively upregulates ATF4 to trigger tumor cell death. Preclinical studies have established the compelling antitumor efficacy of the small molecule in a range of advanced solid tumors as well as its excellent safety profile in animals. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D) in patients with advanced solid tumors. Methods: This open-label study treated 10 patients during the single-patient cohort dose escalation portion of the trial. The human starting dose was 125mg, which represents 1/10th of the no-adverse-adverse-effect-level in animal toxicology studies using standard allometric conversion. Results: The RP2D was defined as 625 mg and no Grade > 1 drug-related adverse events occurred on this trial, which enrolled patients at increasing dose levels of 125mg, 250mg, 375mg, 500mg, and finally 625mg. Pharmacokinetic a...

TPS2623 Background: ONC201 is an orally active first-in-class small molecule with strong antitumor activity in preclinical models of advanced cancers. In cancer cell lines and patient samples ONC20...

e19033 Background: SNX-5422 is an orally bioavailable pro-drug of SNX-2112, a highly potent and selective Hsp90 inhibitor with preclinical anti-tumor activity in lung cancer models and synergy with platinum and taxane compounds. Carboplatin/paclitaxel is a commonly used treatment for advanced lung cancer. This phase 1 study examined SNX-5422 plus carboplatin/paclitaxel followed by SNX-5422 maintenance therapy in pts with advanced lung cancers. Methods: Eligible pts had advanced NSCLC (EGFR wild-type or non-sensitizing mutation, ALK wild-type) or extensive stage SCLC and up to one prior line of chemotherapy. Pts received paclitaxel (175 mg/m2) and carboplatin (AUC 5) q3w up to 4 courses and SNX-5422 qod (starting at 50 mg/m2), 21 of 28 days, with a standard 3+3 dose escalation rule during the combination followed by SNX-5422 (100 mg/m2 qod) monotherapy for maintenance until disease progression. Safety and tolerability were evaluated to determine the maximum tolerated dose (MTD) and pharmacokinetics of SNX-...