You are here
Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: Interim phase I results.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, an IgG1 CTLA-4 checkpoint receptor blocking antibody, have shown activity in advanced NSCLC; clinical data in melanoma showed improved responses and a manageable safety profile when combined. We report interim results from a phase I study evaluating first-line nivolumab + ipilimumab (N+I) in advanced NSCLC patients (pts). Methods: Chemotherapy-naive pts (n=46) with squamous (sq) or non-sq NSCLC received the 3 + 1 mg/kg or 1 + 3 mg/kg combination dose IV Q3W for 4 cycles followed by nivolumab 3 mg/kg IV Q2W until progression/unacceptable toxicity. Objective response rate (ORR; RECIST 1.1) was evaluated overall and by baseline tumor PD-L1 status (Dako immunohistochemistry assay). After an amendment, a 1 + 1 mg/kg cohort was added (n=30, data immature at Dec 2013 analysis). Results: In the 4 cohorts with ≥4 months follow up, any-grade treatment-related adverse events (managed with protocol algorithms) were reported in 39 pts (85%; grade 3–4 in 22 pts [48%]) and led to discontinuation in 16 pts. Treatment-related deaths (n=3) were due to respiratory failure, bronchopulmonary hemorrhage and toxic epidermal necrolysis. Responses occurred in all 4 cohorts (Table); overall ORRb was 22% (median duration of response [mDOR] not reached [NR]) and stable disease (SD) 33% (range 13 – 34.1+ wks); 2 pts exhibited unconventional “immune related” responses. In 29 evaluable tumor samples from the study, ORR did not correlate with PD-L1 status. Conclusions: These interim data in pts with advanced NSCLC suggest that a nivolumab + ipilimumab immunotherapy regimen is feasible and demonstrates antitumor activity in both PD-L1+ and PD-L1– pts. Safety will be further assessed at the 1 + 1 mg/kg dose. The recommended combination dose for phase II/III evaluation has not been determined. Clinical trial information: NCT01454102.
|N1 + I3
|N1 + I3
|N3 + I1
|N3 + I1
|ORR,a n (%)||1 (14)||1 (7)||2 (25)||2 (13)|
|ORR,b n (%)||1 (14)||2 (13)||3 (38)||4 (25)|
|3 (14)||7 (29)|
|SD, n (%)||2 (29)||6 (40)||4 (50)||3 (19)|
|NR (9+)||NR (21+)||17 (12, 21)||NR (24+, 25+)|
|1 (100)||1 (100)||0||2 (100)|
a Confirmed OR only. b Confirmed + unconfirmed OR.
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)