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9554 Background: IMM-101 is a suspension of heat-killed whole cell Mycobacterium obuense (NCTC 13365), which enhances the innate immune response and dendritic cell maturation. In animal models, it increases antigen specific responses and number of CD8+ CTL and CD4 + Th1 cells. The clinical studies with IMM-101 have shown promising efficacy signals in pancreatic cancer when combined with gemcitabine and in melanoma as adjunctive or single agent. Methods: IMM-101-015 is an open-label Phase 2a study to investigate the safety and efficacy of IMM-101 in combination with checkpoint inhibitors (CPIs) in patients (pts) with advanced melanoma who were either treatment-naive (cohort A), or whose disease had progressed during PD-1 blockade (cohort B). Pts with evaluable lesions, adequate performance status and organ function were eligible. Pts received 1.0 mg of IMM-101 every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then every 2 weeks for the next 3 doses, and thereafter every 4 weeks. Nivolumab was given every 2 or 4 weeks (dependent on Investigator choice). Pts in cohort B had the option to change to ipilimumab and IMM-101 if their disease continued to progress. Biopsies and blood samples were obtained at baseline and during treatment for assessment of tumor biomarkers and immune correlatives. The primary objectives of the study were to evaluate the overall response rate (ORR) after a maximum of 18 months of treatment by RECIST 1.1 and to assess the safety and tolerability of the combination of IMM-101 + CPIs. Results: Sixteen pts (11 Cohort A and 5 Cohort B) were treated between October 2018 and May 2021. The median age was 68.5 yrs (range 36-92) and 11 (69%) were male. The ECOG ps was 0 in 9 (56%) and 1 in 7 (44%) pts. Four (25%) had unresectable stage III melanoma and 12 (75%) stage IV. In Cohort A (3 stage III, 5 stage IV M1b and 3 M1c) 3 pts (27%) had an elevated baseline LDH, 6 (55%) a positive PD-L1 status and 3 (27%) a BRAF mutation. Pts in cohort A were on study for a median time of 8.5 months (range 1.5 - 19.1) and those in cohort B for 3.0 months (range 1.5 - 7.4). All pts were evaluated for response. The ORR was 73% (95% CI 39.03, 93.98) in cohort A whereas all pts in cohort B reported progressive disease. With respect to cohort A, 2 (18%) pts had CR, 6 (55%) PR and 1 (9%) SD. The median progression-free survival time was 10.2 months (95% CI 2.50, NE) with 41% of the pts progression-free at 18 months. The most frequent treatment emergent adverse events (TEAEs) were injection site reaction (63%), pruritus (44%), fatigue (38%), skin rash (25%), hypothyroidism (25%) and diarrhoea (19%). There were no grade 4 TEAEs. Grade 3 TEAEs occured in 10 patients (63%), mostly skin toxicity (19%) and lab abnormalities (13%). Conclusions: IMM-101 in combination with nivolumab is safe and shows encouraging antitumor activity in treatment-naive patients with advanced melanoma. Clinical trial information: NCT03711188.

e23141Background: Cancer profiling is receiving increased attention, but comprehensive algorithms to guide targeted and immunotherapies for patients are scarce and complex biomarker data are not ea...

2583 Background: The clinical utility of agents that target EGFR and VEGFR signaling in Non-Small Cell Lung Cancer (NSCLC) is limited by resistance due to emergent alternative growth stimulatory pa...

5572 Background: The PI3K/PTEN/AKT/mTOR pathway is one of the most targeted in human cancers and alterations in the axis are frequent events in squamous cell carcinoma of the head and neck (HNSCC). Specific genetic variations in this pathway have been associated with variation in recurrence, survival and response in lung cancer and esophageal cancer. The aim of this study was to determine whether single nucleotide nucleotide polymorphisms (SNPs) in AKT1, AKT2, FRAP1, PI3KCA and PTEN identified in other cancers were associated with treatment response and clinical outcome in patients with HNSCC. Methods: Genomic DNA was extracted from FFPE tissue specimens of 45 patients with recurrent or initially metastatic HNSCC who received a combined treatment with docetaxel and cetuximab in a phase II study. Eleven single SNPs in the genes AKT1, AKT2, FRAP1 (mTOR), PIK3CA and PTEN were genotyped by means of Real Time PCR system or by direct sequencing and analysed for association with response to therapy and survival. Results: None of the SNPs was related to treatment response. Two SNPs (AKT2:rs8100018 and PTEN:rs12569998) were associated with variation in progression risk. The AKT2:rs8100018 homozygous variant resulted in increased risk, with a HR of 4.83 (95% CI, 1.11-21.03) and the PTEN:rs12569998 homozygous variant in an increased risk, with a HR of 2.36 (95% CI, 1.24-4.50). AKT2:rs8100018 and PTEN:rs12569998 genetic variation had an additive effect on risk of tumor progression. The AKT2:rs8100018 homozygous variant was significantly associated with overall survival (OS) with HR of 3.57 (95% CI, 1.06-12.00) while presence of one of the two variant alleles of AKT1:rs3803304 with a lower risk of death (HR: 0.51; 95% CI, 0.27-0.97). Conclusions: We found significant associations between common genetic variants in the PI3K/PTEN/AKT/mTOR pathway and outcome in patients with HNSCC. Despite the small sample size, patient cohort and treatment were homogeneous. As a consequence, evaluation of SNPs as a host factor may be considered in addition to tumor-specific mutations for personalized treatment development.

e18010 Background: In NSCLC heterogeneity or switch to neuroendocrine phenotype and the expression of stem-cell related markers have been associated with higher tumor aggressiveness. We evaluated the presence of CTC bearing stem cell-related marker CD133+ and the neuroendocrine marker synaptophysin (SYP) in patients with metastatic non small cellular lung cancer (NSCLC). Methods: Forty-four blood samples (20 mL) were collected after informed consent from 16 consecutive patients (pts) with metastatic NSCLC before and during chemotherapy at our Institution. Blood was enriched for tumor cells by CD45 depletion using a magnetic bead separation technique and potential CTC were identified by flow cytometry. CTC were defined as EpCAM+ CK7/8 + CD45-CD53-. Multiparameter cytometry assessed surface expression of the combinations of CD133 and SYP. Results: CTC phenotype: Twenty-five of all 44 samples (57%) were found positive for presence of at least 1 CTC. The median number of CTC was 4 (range: 1-9) / 10mL blood. Twelve samples (27%) showed to be positive for the cancer putative stem cell marker CD133. The median number of CD133+ CTC was 2 (range: 1-7) / 10mL. Seventeen samples (38%) were positive for SYP with a median number of 2 SYN+ CTC (range: 1-6 ) /10ml. Eleven samples (25%) resulted double positive for CD133 and SYP. Tumor heterogeneity: Twelve of the 16 patients (75%) had at least one sample positive for CTC. In 3 pts (25%) CTC expressed only SYP, in 5 pts (42%) both the markers and in 4 pts (33%) neither CD133 nor SYP were expressed. Conclusions: A higher rate of CD133-SYP-double positive CTC compared to the single positive CTC was observed. This suggests that the switch to the neuroendocrine phenotype might occur concomitantly with a stem-cell like more resistant and aggressive phenotype. It needs to be clarified, whether the presence of stem-cell like and neuroendocrine CTC may be a predictive factor for treatment response and outcome in patients with metastatic NSCLC.

e21053 Background: In the majority of cases metastases show an organ-specific pattern of spread. The soil theory states that different organs have special abilities to arrest, attract, and promote ...

e21083 Background: Circulating tumor cell (CTC) quantification has been approved for monitoring of blood from metastatic breast, colon and prostatic cancer patients. In other cancers little is know...

5523 Background: Lymph node metastasis frequently occurs in SCCHN and is generally associated with poor prognosis. The molecular mechanisms regulating tumor cell dissemination and thus the potentia...

8551 Background: Within circulating melanoma cells (CMCs) there may be a subset of cells with stem cell characteristics able to develop distant metastasis. We evaluated the presence of melanoma cel...

e22056 Background: Within circulating tumor cells there may be a subset of cell with stem cell (tumor initiating) characteristics able to develop distant metastasis. Several markers including nestin and CD133 have been found to be possible candidates to identify such a kind of subpopulation in other experimental models. We evaluated the presence of melanoma cells bearing stem cell phenotype in the bloodstream of patients with cutaneous or uveal melanoma after depletion of the leukocytes fraction. Methods: Between 50 and 100 ml of peripheral blood were collected from 12 melanoma patients with various tumor burden as well as three healthy volunteers. Blood samples were enriched for tumour cells by CD45 depletion of the leukocyte fraction using magnetic beads separation (EasySep, Stem Cell Technologies. Inc.). The remaining material was stained with antibodies for the markers Melan-A/Mart-1 (Dako) and HMB45 (Dako), CD133 (Miltenyi Biotec) and nestin (R&D System) and analysed by flow cytometry (BD FACSCalibur). Ten ml of blood were further processed and CD133, nestin, Melan-A/Mart-1 transcripts were quantified by Real Time RT-PCR (LightCycler, Roche Diagnostic). Results: CD45-depleted fractions in healthy controls were negative for melanoma markers. Melan-A/Mart-1 and/or HMB45 positive cells were detectable in 11 out of 12 melanoma patients. The absolute number of melanoma cells identified ranged from 6 to 176 per 10 ml of blood. Nestin expressing cells were more represented compared to CD133 expressing cells (median 27.4%, range 0.3% to 65.1% vs. median 9.3%, range 0.1% to 16.8%) within the melanoma fraction of cells positive for Melan-A/Mart-1 and/or HMB45. In one patient two different melanoma cell populations were detectable. The population of cells with lower expression of the melanoma markers showed at the same time higher expression of nestin and CD133 (5.9% vs. 1.3% and 10.2% vs. 6.7% respectively). Nestin results were in good accordance to the FACS data (nestin: r=0.55; CD133: r=0.23; Pearson test). Conclusions: The novel negative separation technique allows reliable isolation of melanoma cells from peripheral blood of patients with metastatic disease. A significant fraction of melanoma cells in peripheral blood bears a stem cell phenotype. No significant financial relationships to disclose.

7118 Background: Platinum analogues have shown good activity and better toxicity profile than cisplatin/GEM regimens in advanced NSCLC, while sequential administration of two platinum/non-platinum ...