1096P - Prolonged follow-up confirms durability of favorable outcomes after neoadjuvant ipilimumab plus nivolumab in melanoma

Background

A paradigm shift in the treatment of resectable stage III melanoma is expected, given the superior results of neoadjuvant (neoadj) immune checkpoint inhibition (ICI) in the SWOG S1801 trial and with the 1st phase III trial (NCT04949113) on its way. In this rapidly evolving field, long-term outcomes of neoadj ICI are scarce. Here we report the 4- and 6-yr survival update of the OpACIN and OpACIN-neo.

Methods

In the randomized OpACIN trial, 20 patients (pts) with resectable stage III melanoma were treated with ipilimumab (IPI) 3mg/kg + nivolumab (NIVO) 1mg/kg; in the adjuvant (adj) arm 4 cycles after therapeutic lymph node dissection (TLND) and in the neoadj arm 2 cycles before and 2 after TLND. In the OpACIN-neo trial, 86 pts were randomized between neoadj IPI 3mg/kg + NIVO 1mg/kg (2x; arm A), IPI 1mg/kg + NIVO 3 mg/kg (2x; arm B) and IPI 3mg/kg (2x) > NIVO 3mg/kg (2x; arm C), followed by TLND without adj therapy. Event-free survival (EFS) was defined as time from randomization to progression, recurrence or death.

Results

Median follow-up (FU) for OpACIN was 84.0 mo. Estimated 6-yr EFS was 60% for both the adj and neoadj arm, while OS was 70% and 90% respectively. Only 1 recurrence has been observed after the 3-yr landmark. Median FU for OpACIN-neo was 60.7 mo. Estimated 4-yr EFS was 80% (see table for EFS/OS). After the 3-yr landmark, 1 new recurrence was observed and 1 non-melanoma related death. Major- and partial pathological responders (MPR/pPR) had 4-yr EFS rates of 96% and 92%, versus 33% in non-responders (pNR). Combining data from both trials, the median time to recurrence was 6.2 mo for the 16 pts that relapsed after pNR, while this was 37.7 mo for the 3 pts that relapsed after MPR/pPR. Table: 1096P

Conclusions

Although the EFS rates are similar for the neoadj and adj arms after 6 yrs in the OpACIN trial, the favorable EFS and OS rates observed in the larger OpACIN-neo support the durability of response to neoadj IPI plus NIVO. The pathological response may serve as predictor for long-term outcome.

Clinical trial identification

NCT02437279; NCT02977052.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol Myers Squibb.

Disclosure

A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre Fabre, QBiotics. B. van de Wiel: Financial Interests, Institutional, Advisory Role: BMS. R. Scolyer: Financial Interests, Institutional, Advisory Role: F. Hoffmann-La Roche Ltd., Evaxion, Provectus Biopharmaceuticals Australia, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen Inc., Bristol Myers Squibb, Myriad Genetics, GSK. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharp & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharp & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. G.V. Long: Financial Interests, Institutional, Advisory Role: Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics, Innovent Biologics, MSD, Novartis, OncoSec, PHMR Ltd., Pierre Fabre, Provectus, QBiotics, Regeneron Pharmaceuticals. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Advisory Board: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Immagene; Financial Interests, Institutional, Coordinating PI: NanoString, BMS, Novartis, 4SC; Financial Interests, Personal, Stocks/Shares, intention to develop IFN signature algorithm: NewCo, no name yet; Other, pending patent: WO 2021/177822 A1. All other authors have declared no conflicts of interest.