You are here
Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer (NSCLC).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: First-line PT-DC has demonstrated 1-yr overall survival (OS) rates of up to 54% in NSCLC; however, there remains a need for therapies with improved long-term survival. We report an updated analysis of a phase I multi-cohort study evaluating nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, plus PT-DC in chemotherapy-naive patients (pts) with advanced NSCLC, with longer follow up and additional pts. Methods: Pts (N=56) with advanced NSCLC were assigned based on histology to 4 cohorts to receive nivolumab 10 mg/kg IV Q3W plus concurrent IV gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2 (squamous [sq]) or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 (non-sq), or nivolumab 5 or 10 mg/kg IV Q3W plus IV paclitaxel 200 mg/m2+ carboplatin AUC6 (sq + non-sq), in a phase I dose de-escalation trial to assess dose-limiting toxicity (DLT). PT-DC was given for 4 cycles, followed by nivolumab until progression or unacceptable toxicity. Objective response rate (ORR) was assessed by RECIST 1.1. Results: No DLTs were seen during the first 6 wks of treatment. Grade 3-4 treatment-related adverse events were reported in 45% of pts (25-73% across arms), including pneumonitis (4 pts, 7%; managed by protocol algorithm), and fatigue and acute renal failure (3 pts [5%] each). Across arms, ORR (≥10 months follow up) was 33–50% and progressive disease (PD) as best overall response (BOR) was infrequent (Table). One-year OS rates were 59–87% (Table). Conclusions: Nivolumab combined with standard PT-DC regimens used for first-line treatment of NSCLC demonstrated antitumor activity, with encouraging 1-yr OS and an acceptable tolerability profile. Clinical trial information: NCT01454102.
|Nivo 10 + gem/cis
|Nivo 10 + pem/cis
|Nivo 10 + pac/carb
Sq + Non-sq
|Nivo 5 + pac/carb
Sq + Non-sq
|ORR, a n (%)||4 (33)||7 (47)||7 (47)||7 (50)|
|Median duration of response
(Kaplan-Meier),a wk (range)
|PD as BOR, n (%)||0||0||3 (20)||1 (7)|
|PFS rate wk 24, %||36||71||38||57|
|1-yr OS, %||59||87||59||Insufficient
a Confirmed responses only. + Ongoing.
Abstracts by Scott Joseph Antonia:
A phase III study (CheckMate 017) of nivolumab (NIVO; anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC).Meeting: 2015 ASCO Annual Meeting | Abstract No: 8009
Activation of CD8+ tumor infiltrating lymphocytes by bavituximab in a 3D ex vivo system of lung cancer patients.Meeting: 2015 ASCO Annual Meeting | Abstract No: 3060
Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): update from a phase Ia study.Meeting: 2015 ASCO Annual Meeting | Abstract No: 8029
Presentations by Scott Joseph Antonia:
Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032.Meeting: 2015 ASCO Annual Meeting Abstract No: 7503Session: Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers (Oral Abstract Session)