972O - Nivolumab (Nivo) plus ipilimumab (Ipi) 6-months treatment versus continuation in patients with advanced non-small cell lung cancer (aNSCLC): Results of the randomized IFCT-1701 phase III trial

Background

1^st-line immunotherapy (io) is a standard treatment for patients (pts) with aNSCLC and no targetable mutation. Classical 2-years io duration does not rely on solid evidence. We aimed to assess whether 6-months nivo/ipi duration was equivalent to continuation until progression in pts with disease control (DC).

Methods

In this multicenter non-inferiority randomized phase III trial, eligible pts treatment-naive, age>18, PS 0-1, had histologically proved stage IV NSCLC and measurable disease. They received Nivo 3 mg/kg q2w plus Ipi 1 mg/kg q6w, until progression or unacceptable toxicity. At 6 months, pts with DC and no severe TRAEs were randomized (1:1) into arm A, io continuation, and arm B, observation. At progression, arm A pts received an investigator's choice 2^nd line platinum-based chemo, while arm B pts resumed double io. Primary endpoint was progression-free survival (PFS). 450 pts x 2 were to be randomized, to achieve 80% power, with 0.025 one-sided an error. Observing that European filing for the io combo was not submitted, the trial steering committee decided to stop the accrual on Jan. 15^th 2021.

Results

From May. 2018 to Jan. 2021, 265 pts (70.6% male, 62.7y median age, 60% stage IVB, 22.3% SCC, 9.9% PDL1≥50%, 12.2% PDL1<1%) were accrued. 137 (72.1%) pts showed disease progression before 6 months, 11 died (5.8%), 29 (15.3%) experienced TRAEs contra-indicating continuation, 13 (6.8%) were deemed ineligible for randomization. 71 pts with DC were randomized. With a median 21.0 months follow-up from randomization, median PFS was 20.8 (8.3-NR) months in arm A, not reached (17.7-NR) in arm B pts. 12-months PFS was 57.1% (39.3-71.5) and 77.6% (58.7-88.7) in arm A and B respectively (p=0.09). Adj.HR (arm B vs. arm A) was 0.65, 95%CI (0.29-1.49), p=0.31. OS yet immature data did not show significant difference between both arms (adj. HR arm B vs. A: 0.52 95%CI (0.13-2.12), p=0.36). No significant difference in G3-5 iTRAEs rate was observed.

Conclusions

The non-significant PFS difference between the 6-months and the continuation arms is hypothesis generating since data are underpowered due to trial premature halt.

Clinical trial identification

EudraCT: 2017-002540-33; NCT03469960.

Editorial acknowledgement

Legal entity responsible for the study

IFCT.

Funding

IFCT BMS.

Disclosure

G. Zalcman: Non-Financial Interests, Personal, Other, Invitations, travel and housing for international meetings: Roche, MSD, BMS, AstraZeneca, Lilly, Pfizer, AbbVie; Financial Interests, Personal, Advisory Board: Lilly, AstraZeneca, BMS, Pfizer, Roche, MSD, Boehringer Ingelheim, Inventiva, Paredox Therapeutics; Financial Interests, Institutional, Principal Investigator: Lilly, GSK, Roche, MSD, Merck-Serono, Pfizer, AstraZeneca, Sanofi-Aventis, Pierre Fabre, Boehringer Ingelheim, BMS, Novartis, Ariad, Takeda. A. Madroszyk Flandin: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche; Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Personal, Other: MSD. D. Debieuvre: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Janssen, Pfizer, Ose Immunotherapeutics, Novartis, Sanofi-Aventis, Amgen, Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugai, Chiesi, Novartis, Takeda, Bayer, Sanofi-Aventis. E. Pichon: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche. E. Giroux-Leprieur: Financial Interests, Personal, Advisory Board: BMS. N. Cloarec: Financial Interests, Personal, Advisory Board: Takeda. V. Westeel: Financial Interests, Personal, Other, Scientific committee and invited speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, advisory board, scientific committee and invited speaker: MSD; Financial Interests, Personal, Advisory Board: Takeda, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Institutional, Other, local PI and steering committee member: Bristol Myers Squib; Financial Interests, Institutional, Invited Speaker: MSD, Roche; Other, support for meeting attendance: AstraZeneca, Bristol Myers Squib, Sanofi. A.C. Toffart: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Non-Financial Interests, Personal, Other, Invitation to congress: AstraZeneca, Roche. All other authors have declared no conflicts of interest.