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Alejandro Navarro
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FP10 - Small Cell Lung Cancer/NET (ID 231)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP10.04 - RESILIENT Part 1: Safety and Efficacy of Second-Line Liposomal Irinotecan in Patients with Small Cell Lung Cancer (ID 3657)
00:00 - 00:00 | Author(s): Alejandro Navarro
- Abstract
- Presentation
Introduction
Many patients with small cell lung cancer (SCLC) develop drug resistance to first-line platinum-based chemotherapy, and second-line therapies are limited. RESILIENT (ClinicalTrials.gov identifier NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of liposomal irinotecan monotherapy as second-line treatment for patients with SCLC. Here we report data from part 1 of the RESILIENT study (data cut off, 2 December 2019).
Methods
RESILIENT part 1 was an open-label, single-arm study comprising dose-exploration and dose-expansion phases. Eligible patients with SCLC were aged ≥ 18 years, had progressed with platinum-based first-line therapy, had an Eastern Cooperative Oncology Group performance status score of 0 or 1, and had adequate organ function; prior exposure to immunotherapy was permitted. During dose exploration, participants received liposomal irinotecan 85 mg/m2 or 70 mg/m2 free base administered every 2 weeks; the identified recommended dose was used during dose expansion. Primary endpoints were safety and tolerability. Efficacy assessments included objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), and overall survival (OS).
Results
In total, 30 patients received liposomal irinotecan in RESILIENT part 1 (women, 56.7%; median age, 61.5 years). During dose exploration, four patients who received liposomal irinotecan 85 mg/m2 experienced dose limiting toxicities, including diarrhea (n = 3) and abnormal liver function test (n = 1). Thus, this dose was not considered tolerable and enrollment into the 70 mg/m2 cohort was initiated; a total of 25 patients (platinum resistant, 40%) received liposomal irinotecan 70 mg/m2 (dose exploration, 12 patients; dose expansion, 13 patients). Among the 25 patients who received the recommended dose of 70 mg/m2, 40% had one or more grade ≥ 3 treatment-related treatment-emergent adverse events (TEAEs), most commonly diarrhea (20%), neutropenia (16%), and anemia, thrombocytopenia, asthenia and abdominal sepsis (each 8%); 8% of patients discontinued treatment owing to TEAEs. Median (95% CI) PFS was 3.98 (1.45–4.24) months and OS was 8.08 (5.16–9.82) months. ORR (complete response + partial response) was 44% and BOR was: complete response, 4%; partial response, 40%; stable disease, 28%; progressive disease, 20%; non-evaluable, 8%.Thirty patients were treated in RESILIENT part 1. Full results to be presented in the updated abstract.
Conclusion
In participants with SCLC who had progressed with platinum-based first-line therapy, liposomal irinotecan at the recommended dose of 70 mg/m2 showed promising antitumor activity and safety findings were aligned with the known safety profile. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial versus topotecan will provide further data regarding the efficacy and safety of liposomal irinotecan 70 mg/m2 for the second-line treatment of 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): Alejandro Navarro
- 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.
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P24 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Mesothelioma Clinical and Trials in Progress (ID 138)
- Event: WCLC 2020
- Type: Posters
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 01:00, ePoster Hall
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P24.06 - Real World use of Cisplatin and Carboplatin Based Therapy in Patients with Malignant Pleural Mesothelioma (MPM) (ID 3014)
00:00 - 01:00 | Author(s): Alejandro Navarro
- Abstract
Introduction
MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Cisplatin with pemetrexed or raltritexed is standard first line. There are no randomized trial comparing cisplatin versus carboplatin in MPM however, carboplatin is often substituted to decrease toxicity. The objective of this study is to characterize the impact of cisplatin use on survival in p diagnosed with MPM at our institution
Methods
We review 189 MPM p diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method.
Results
Patient’s characteristics: median age 68 years (y) (29-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 74%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed) and 19 p were treated in clinical trials in first line. Median progression free survival (PFS) was 4.4 months (m;CI95% 3.1-5.4). Median survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS. Patients treated with cisplatin in first line were younger (64 vs 74 y p with carboplatin), and with more epithelioid tumors (81% vs 73%). No differences in median number of cycles were found (5 cycles for cisplatin and 5 cycles for carboplatin). Regarding the moment of cisplatin initiation, better survival was found in p receiving cisplatin in first or second line. Median OS for p treated with cisplatin in first line was 23.1m vs 16.4 m for p treated with carboplatin (95%CI 0.3-0.7). Second line was given in 58% of p (13% with cisplatin based and 32% with carboplatin based). In second line median OS for cisplatin treated p was 43.7 vs 18.5 m (95%0.12-1.9) and combinations platinum based were associated with better survival compared with no-platinum treatments (mOS 17.1 platinum-based vs 10.7 no-platinum, 95% 0.32-0.8)
Conclusion
In our real-world experience, carboplatin is an acceptable first line option in p who may not be able to tolerate cisplatin. However, in our series cisplatin combinations are associated with superior outcome in first and second line.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.06 - Lurbinectedin in Combination with Pembrolizumab for Patients with Relapsed Small Cell Lung Cancer. LUPER Clinical Trial (ID 3669)
00:00 - 00:00 | Author(s): Alejandro Navarro
- Abstract
Introduction
Small cell lung cancer (SCLC) cells are highly dependent on oncogenic transcription factors (TF) such as ASCL1, NeuroD1 and NFIB, which support their growth. Lurbinectedin is a selective transcription protein-coding gene inhibitor, that causes the detachment of TF from target promoters. Moreover, in vivo studies have shown lurbinectedin affects the inflammatory microenvironment, by inducing a pro-apoptotic effect on tumor-associated macrophages (TAMs) and a specific inflammatory cytokines inhibition of production. Lurbinectedin was approved by the FDA for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy based on a single-arm, open-label study phase 2 basket trial.. The aim of this phase I/II study is to assess the safety, tolerability and preliminary efficacy of lurbinectedin in combination with pembrolizumab for the treatment of pts with SCLC in second line after relapse or progressive disease. The phase I stage is a dose escalation to select the recommended dose (RD) based on the safety observed after the administration of lurbinectedin in combination with pembrolizumab. The phase II stage will explore the clinical activity at the RD.
Methods
This is a multicenter, open-label, single-arm, phase I/II study of lurbinectedin (iv) in combination with pembrolizumab (iv) in pts with relapsed or progressive SCLC (NCT04358237). In the phase I, cohorts of 3-6 pts with SCLC will be treated with escalating doses of PM01183 in combination with a fixed dose of pembrolizumab. In the phase II stage, a single expansion cohort of approximately 30 pts will be treated with lurbinectedin combined with pembrolizumab at the recommended dose (RD) determined during the phase I stage. Regardless of stage, pts will receive lurbinectedin in combination with pembrolizumab until progression, unacceptable toxicity, consent withdrawal or if not considered in their best interest to continue. Main inclusion criteria include: (a) pts with histologically confirmed diagnosis of SCLC whose disease has progressed after first-line chemotherapy-based regimen, (b) at least 4 weeks since the last anticancer therapy, (c) measurable or evaluable disease according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v 1.1). Recruitment: 30 evaluable pts in the RD will be recruited to test the null hypothesis, 10% or less pts will respond, versus the alternative hypothesis, 30% or more pts will respond to treatment. Primary objectives: (i) the determination of maximum tolerated dose (MTD) and RD, and dose-limiting toxicities (DLTs) of lurbinectedin in combination with pembrolizumab, and (ii) to assess the efficacy of lurbinectedin in combination with pembrolizumab. Secondary objectives include: (i) to obtain preliminary information on clinical antitumor activity of this combination in pts with SCLC, (ii) to characterize antitumor activity of this combination as per RECIST 1.1 in terms of overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS), (iii) to characterize the safety profile and the plasma pharmacokinetics (PK) of the combination, (iv) to perform pharmacogenetic (PGt) and pharmacogenomic (PGx) analysis in tumor samples of pts. Current status active, not yet recruiting.
