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A. Atmaca
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.05 - Nivolumab Alone or with Ipilimumab in Recurrent Small Cell Lung Cancer (SCLC): 2-Year Survival and Updated Analyses from the Checkmate 032 Trial (ID 4397)
14:50 - 14:56 | Author(s): A. Atmaca
- Abstract
- Presentation
Background:
Patients with SCLC and disease progression during/after first-line platinum-based chemotherapy have poor prognoses and limited treatment options. Nivolumab alone and in combination with ipilimumab has shown survival benefit and durable responses in multiple tumor types. Here we present updated results for the SCLC cohort of the phase 1/2 CheckMate 032 trial (NCT01928394), which was designed to evaluate nivolumab or nivolumab/ipilimumab in advanced solid tumors.
Methods:
Patients with advanced SCLC that progressed following ≥1 platinum-based chemotherapy regimens were assigned to receive nivolumab monotherapy (nivolumab-3 Q2W) or nivolumab/ipilimumab combination therapy (nivolumab-1/ipilimumab-3 or nivolumab-3/ipilimumab-1 Q3W for 4 cycles, then nivolumab-3 Q2W). Patients were eligible regardless of platinum sensitivity or tumor programmed death ligand 1 (PD-L1) expression. The primary endpoint was ORR. Additional endpoints were duration of response (DOR), OS, PFS, safety, and correlation of tumor PD-L1 expression with activity.
Results:
214 patients have been enrolled to date (nivolumab-3, n=98; nivolumab-1/ipilimumab-3, n=61; nivolumab-3/ipilimumab-1, n=55), including 96 and 118 patients treated with 1 or ≥2 prior regimens, respectively. Efficacy and safety data are shown (table). In the nivolumab-1/ipilimumab-3 cohort, ORR was 23% and 1-year OS was 43%. The proportion of patients with PD-L1–expressing tumors was substantially lower in previously treated SCLC in this study than that previously observed with pretreated NSCLC (16% vs 53%–54% with ≥1% PD-L1 expression). In SCLC, responses were observed regardless of PD-L1 expression. ORR and median OS were similar in patients treated with 1 or ≥2 prior regimens. Rate of discontinuation due to treatment-related AEs ranged from 5% to 11%; there were 3 treatment-related deaths. Figure 1
Conclusion:
Durable objective responses were observed with nivolumab and nivolumab/ipilimumab in patients with previously treated SCLC, and safety profiles were consistent with other tumor types. Updated efficacy (including 2-year OS and DOR), safety, and additional subgroup analyses will be presented from the August 2016 DBL.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-011 - Phase 2 Study of MM-121 plus Chemotherapy vs. Chemotherapy Alone in Heregulin-Positive, Locally Advanced or Metastatic NSCLC (ID 4158)
14:30 - 14:30 | Author(s): A. Atmaca
- Abstract
Background:
The role of the HER3 receptor and its ligand heregulin (HRG) in the progression of multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal IgG2 antibody that binds to the HRG domain of HER3, blocking HER3 activity. The correlation between the level of HRG mRNA in tumor tissue and progression free survival (PFS) were retrospectively analyzed in three completed randomized Phase 2 studies of seribantumab plus standard of care (SOC) versus SOC alone (NSCLC, breast cancer and ovarian cancer). In each of these studies, high levels of HRG mRNA predicted shortened PFS for patients who received SOC treatment, while the addition of seribantumab to SOC improved PFS for patients with HRG-positive (HRG+) tumors. This is consistent with the hypothesis that HRG expression defines a drug tolerant cancer cell phenotype shielded from the effects of cytotoxic or targeted therapies and that blockade of HRG-induced HER3 signaling by seribantumab counters the effects of HRG on cancer cells, with the potential to improve outcomes for HRG+ patients. It is estimated that up to approximately 50% of cases of all solid tumor indications are HRG+. This HRG expression may contribute to rapid clinical progression in a subset of patients with poor prognosis.
Methods:
In the ongoing randomized, open-label, international, Phase 2 study, NSCLC patients with HRG+ tumors are being prospectively selected using a HRG RNA in situ hybridization assay performed on a recent tumor tissue sample collected via fine needle aspiration, core needle biopsy or excision. Approximately 560 patients will be screened to support enrollment of 280 HRG+ patients, who will be randomized in a 2:1 ratio to receive seribantumab plus investigator’s choice of docetaxel or pemetrexed, or docetaxel or pemetrexed alone. Patients will be wild-type for EGFR and ALK and will have progressed following one to three systemic therapies, one of which must be an anti-PD-1 or anti-PD-L1 therapy, for locally advanced and/or metastatic disease. Overall survival (OS) is the primary endpoint of the study and secondary endpoints include PFS, objective response rate and time to progression. Safety and health-related quality of life will also be assessed. An interim analysis is planned when 50% of final OS events have been reported. Enrollment has been initiated with approximately 80 sites expected to participate worldwide. Clinical Trials Registry number: NCT02387216
Results:
Section not applicable
Conclusion:
Section not applicable
