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Rosalyn Juergens



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    FP03 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) (ID 151)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP03.03 - Clinical Activity of BMS-986012, an Anti–Fucosyl-GM1 Monoclonal Antibody, Plus Nivolumab in Small Cell Lung Cancer (ID 3396)

      00:00 - 00:00  |  Author(s): Rosalyn Juergens

      • Abstract
      • Presentation
      • Slides

      Introduction

      In patients with extensive-stage small cell lung cancer (ES-SCLC), the addition of an anti–PD-L1 regimen to chemotherapy demonstrated limited benefit, with an increase in survival by 2 months (Horn et al. N Engl J Med. 2018;379:2220–2229). Therefore, future prospects for better outcomes in SCLC lie in novel medicines and new treatment combinations. Fucosyl-GM1 is a monosialoganglioside expressed in 50%–70% of SCLC with limited expression in normal tissues (Brezicka et al. APMIS. 1991;99:797–802; Brezicka et al. Tumour Biol. 1992;13:308–315). BMS-986012 is a nonfucosylated, fully human monoclonal antibody with high binding specificity for fucosyl-GM1 engineered to enhance antibody-dependent, cell-mediated cytotoxicity (Ponath et al. Clin Cancer Res. 2018;24:5178–5189). We previously reported that the combination of BMS-986012 and nivolumab in patients with relapsed/refractory SCLC was well tolerated and demonstrated preliminary antitumor activity (Chu et al. Ann Oncol. 2017;28(suppl 5). Abstract 1528PD). Here, we report updated safety and antitumor activity results from the phase 1/2 trial of the combination of BMS-986012 and nivolumab in patients with relapsed/refractory SCLC (NCT02247349).

      Methods

      Patients with relapsed/refractory SCLC who had not received prior checkpoint inhibitor (CPI) therapy received BMS-986012 400 or 1000 mg with nivolumab 360 mg intravenously every 3 weeks. The primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and pharmacokinetics. Median overall survival (mOS) was an exploratory endpoint.

      Results

      As of July 22, 2020, 29 patients received BMS-986012 (400 mg, n=21; 1000 mg, n=8) with nivolumab, with a follow-up of 18.6 months (range, 0.6–41.1 months). Median age of patients was 65 years (range, 46–79 years) and 52% were male; ECOG performance status was 0 (38%) or 1 (62%). The combination was well tolerated, with manageable adverse effects. The most common all-grade/grade ≥3 treatment-related adverse events were pruritus (93%/21%), fatigue (28%/0%), dry skin (28%/0%), and hypothyroidism (17%/0%). In most patients, pruritus diminished over time and was managed with antihistamines and low-dose corticosteroids. Confirmed ORR with BMS-986012 plus nivolumab was 38% (CR, n=1 [3%]; PR, n=10 [35%]), with 3 additional patients (10%) having SD, for an overall disease control rate of 48%. At data cutoff, mDOR was 26.4 months (95% CI, 4.4 months–NR); 4 patients were still on therapy. mPFS was 2.1 months (95% CI, 1.4–9.9 months) and mOS was 18.7 months (95% CI, 8.2 months–NR). No differences in response were noted between platinum-sensitive and refractory populations.

      Conclusion

      The results presented here suggest that BMS-986012 plus nivolumab is a promising therapeutic combination for the treatment of patients with relapsed/refractory SCLC not previously treated with CPI therapy, irrespective of whether their cancers were platinum sensitive or refractory. The safety profile was manageable, and although based on a small number of patients, responses were clinically meaningful and durable. These updated data warrant further investigation of this combination in patients with SCLC.

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    P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P89.03 - Demonstrating VALUE of Liquid Biopsy for Lung Cancer in a Public Healthcare System (ID 2333)

      00:00 - 00:00  |  Author(s): Rosalyn Juergens

      • Abstract
      • Slides

      Introduction

      Liquid biopsy (LB) is an important alternative for advanced lung cancer patients in diagnosing resistance or where tissue genotyping has failed. The VALUE study examines clinical outcomes and utility of LB for molecular diagnosis in treatment naive stage IV lung adenocarcinoma patients.

      [Preliminary data previously presented at ASCO2020. Final study results will be available for WCLC2021]

      Methods

      This study is being conducted at 6 Canadian centres (NCT03576937) using Guardant360TM (G360), a validated cell-free DNA next-generation sequencing assay that identifies variants in 74 cancer-associated genes, including fusions and copy number gain. Patients with treatment-naïve advanced non-squamous lung carcinoma, ≤10 pack-year smoking history, and measurable disease are eligible (N=150). Patients receive standard of care tumour tissue (TT) molecular profiling (EGFR, ALK +/- ROS1) and LB. The primary endpoint is response rate to first-line therapy (RECIST 1.1); secondary endpoints include incremental targetable alterations identified through G360 (EGFR, ALK, BRAF, ERBB2, KRAS (G12C), NTRK, MET (amplification, exon 14 skipping), RET, ROS1), turnaround time (TAT) and successful molecular profiling rates.

      Results

      To date, 150 eligible patients have been enrolled. Demographic data are available for the first 100 patients, treatment data for 89 and 60 have response data. Median age is 63 (range 22-91), 63% are female, 85% never smokers, 35% East Asian, 24% ECOG PS>1, and 94% have adenocarcinoma. Actionable targets have been identified in 55% of patients using G360 (EGFR/ALK in 38%), and 38% using standard TT profiling. Concordance between TT and LB was high, 84%, with 8 cases each identified by TT or LB but not the other. TT profiling for EGFR/ALK was unsuccessful in 6% of patients (insufficient tissue, failed biopsy, single biomarker tested only). Fifteen patients (15%) had no ctDNA alterations detected by G360 (low disease burden vs. non-shedding). Of 89 patients receiving first-line treatment, 60% received targeted therapy, 26% chemo-immunotherapy combinations, 10% checkpoint inhibitors alone and 4% were observed. Treatment decisions were informed by G360 alone in 40% and by G360+TT results in 28% (by physician report). Among 51 evaluable patients, ORR was 55% (28/51). Using G360, ORR was 75% (18/24) in those with actionable alterations and 37% (10/27) in those without. Using TT, ORR was 64% (16/25) in those with actionable alterations and 46% (12/26) in those without. Mean TAT was 7.7 days (SD+/-1.6) for LB vs 20.8 days (SD+/- 9.8) for TT.

      Conclusion

      LB using G360 identifies actionable targets beyond tissue profiling alone in newly diagnosed lung cancer patients, has faster TAT and yields similar outcomes with targeted and non-targeted therapy.

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