2528 - CheckMate 592: a phase 2 exploratory study of biomarkers associated with the efficacy of first-line nivolumab (nivo) plus ipilimumab (ipi) in patients (pts) with stage IV or recurrent NSCLC

Background

Combining PD-1 and CTLA-4 inhibitors can augment antitumor immune responses. In the phase 1 CheckMate 012 study, first-line nivo (anti–PD-1 antibody) plus ipi (anti–CTLA-4 antibody) exhibited a higher objective response rate (ORR) and 2-year overall survival (OS) rate than nivo alone in pts with stage IIIB/IV NSCLC. Pts whose tumors expressed PD-L1 or had a high tumor mutational burden (TMB) showed better outcomes. High TMB was identified in the phase 2 CheckMate 568 (nivo + ipi) and phase 3 CheckMate 026 (nivo alone) studies and validated in phase 3 CheckMate 227 (nivo + ipi) as a potential predictive biomarker, independent of PD-L1 expression. High TMB may result in high expression of neoantigens, which could prime responses to checkpoint inhibitors. Beyond PD-L1 and TMB, there may be other important potential predictive biomarkers. CheckMate 592 (NCT03001882) is a two-part, exploratory, open-label phase 2 study exploring potential biomarkers, including PD-L1 and TMB, among others, and their association with clinical benefit with first-line nivo + ipi for stage IV or recurrent NSCLC.

Trial design

Pts aged ≥18 years with treatment-naïve stage IV or recurrent NSCLC and who had ECOG performance status 0–1 are being enrolled in the United States (parts 1 and 2) and Europe (part 2). Pts are ineligible if they have active autoimmune disease. In part 1, approximately 100 pts will be analyzed according to PD-L1 status (≥1% vs < 1%) before treatment. In part 2, approximately 150 pts will be treated regardless of PD-L1 status. The primary endpoint in part 1 is the association of ORR with baseline TMB, and candidate peripheral blood and tumor biomarkers at baseline and on treatment; secondary endpoints are ORR, disease control rate, response duration, time to response, progression-free survival (PFS), OS, and the association of enteric biomarkers with efficacy. Primary endpoints in part 2 are the association of ORR with baseline tissue and blood TMB; secondary endpoints are ORR, PFS, OS, safety, and the association of enteric biomarkers with efficacy. The start date was March 2017. The estimated primary completion date is March 2019.

Clinical trial identification

NCT03001882.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Editorial Acknowledgement

Professional medical writing and editorial assistance were provided by StemScientific, funded by Bristol-Myers Squibb.

Disclosure

S. Gettinger: Research funding: Bristol-Myers Squibb, Genentch, Ariad, Incyte, Pfizer, and Celldex; Consulting fees: Bristol-Myers Squibb, Ariad, Pfizer, and Alexion Pharmaceuticals. X. Yang: Payment to institution: Bristol-Myers Squibb for clinical trial services. D. Morgensztern: Consultant: Abbvie and Bristol-Myers Squibb. V. Velcheti: Consultant: Merck, Bristol-Myers Squibb, Genentech, and AstraZeneca. S.S. Ramalingam: Advisory board meetings: AstraZeneca, Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Lilly, Merck, Genentech, Roche and Takeda. K. Schalper: Grants: Navigate Biopharma, Vasculox/Tioma, Tesaro Inc., Onkaido/Moderna, Takeda, Surface Oncology and Pierre-Fabre; Consultant: Celgene, Shattuck Labs and Moderna Therapeutics. M. Dajee, A. Ranck, R. Yang: Stock ownership and employee: Bristol-Myers Squibb. D.R. Spigel: Consulting role: Novartis and Genentech; Travel, accommodations, and expenses: Novartis, Genentech, and Pfizer. All other authors have declared no conflicts of interest.