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Deanne Lathers
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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): Deanne Lathers
- Abstract
- Presentation
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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P15 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Phase I) (ID 154)
- Event: WCLC 2020
- Type: Posters
- 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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P15.06 - Safety of BMS-986012, an Anti–Fucosyl-GM1 Monoclonal Antibody Plus Platinum/Etoposide in Untreated Extensive-Stage SCLC (ID 3416)
00:00 - 00:00 | Author(s): Deanne Lathers
- Abstract
Introduction
Small cell lung cancer (SCLC) is an aggressive lung tumor, with patients often presenting with metastatic disease at the time of diagnosis. Treatments for patients with extensive-stage SCLC have advanced little over the years, with 5-year overall survival (OS) rates remaining dismal. Immunotherapy has demonstrated clinical activity in ES-SCLC; however, the OS improvements have been only modest, with the first-line population remaining an unmet need in terms of treatment options (Horn et al. N Engl J Med 2018;379:2220–2229; Paz-Ares et al. Lancet 2019;394:1929–1939). Fucosyl-GM1, a tumor-associated antigen, is expressed in 50%–70% of cases with limited expression on normal tissue (Brezicka et al. Cancer Res 1989;49:1300–1305; Zhang et al. Int J Cancer 1997;73:42–49). Therefore, fucosyl-GM1 constitutes a potential target in SCLC. BMS-986012, a novel, first-in-class, nonfucosylated, fully human monoclonal antibody with high binding specificity for fucosyl-GM1 and enhanced antibody-dependent cellular cytotoxicity (Ponath et al. Clin Cancer Res 2018;24:5178–5189), was well tolerated and demonstrated promising antitumor activity in patients with relapsed/refractory SCLC (Chu et al. Ann Oncol 2016;27[suppl 6]. Abstract 1427PD). Here, we report the preliminary safety findings from a phase 1/2 trial of the combination of BMS-986012 and platinum/etoposide followed by BMS-986012 monotherapy maintenance in previously untreated patients with extensive-stage SCLC (NCT02815592).
Methods
Patients received BMS-986012 400 mg or 1000 mg on day 1, combined with either cisplatin 80 mg/m2 (part 1) or carboplatin area under the curve (AUC) 5 (part 2) on day 1 plus etoposide 100 mg/m2 on days 1, 2, and 3 (both parts) over four 21-day cycles, followed by BMS-986012 monotherapy maintenance. The primary endpoint was safety.
Results
As of Feb 6, 2020, 14 patients had received BMS-986012 (400 mg, n=12; 1000 mg, n=2) combined with platinum/etoposide, with 11 patients continuing into the monotherapy period. The median age was 62 years (range, 49–81 years), and 11 patients (79%) were men. BMS-986012 in combination with platinum/etoposide was well tolerated, and most treatment-related adverse events (TRAEs) were grade 1–2. The most common TRAEs (all grade; grade ≥3) was pruritus (86%; 7%). In most cases, pruritus resolved with antihistamines or low dose corticosteroids. Urticaria (7%; 7%), neutropenia (7%; 7%), xerosis (7%; 0%), conjunctivitis (7%; 0%), infusion-related reaction (7%; 0%), and dizziness (7%; 0%) were also observed. No serious TRAEs or dose-limiting toxicities were reported. One patient (BMS-986012 400 mg/carboplatin/etoposide) discontinued due to acute coronary syndrome determined to be unrelated to treatment. No notable differences were observed in the safety profiles of BMS-986012 plus cisplatin/etoposide (n=7) and BMS-986012 plus carboplatin/etoposide (n=7) in this study.
Conclusion
BMS-986012 in combination with platinum/etoposide was well tolerated in a treatment-naive patient population with extensive-stage SCLC. The safety profile was comparable to the profile observed historically with platinum/etoposide chemotherapy alone, except for clinically manageable pruritis. The safety findings support the ongoing evaluation of BMS-986012 as first-line therapy for extensive-stage SCLC.
