Abstract 1097P
Background
Neoadjuvant (neoadj) IPI + NIVO showed in different trials in almost 200 patients (pts) a pathologic response rate of 71-78%. The investigator-initiated OpACIN trial was the first trial testing neoadj IPI + NIVO and therefore has the longest follow-up (FU). Pathologic responses were observed in 7/9 pts (78%) in the neoadj arm, 1 pt was non-evaluable. The question remains how durable these responses are. Here we present the 4-year safety and survival data from this trial.
Methods
Twenty macroscopic stage IIIB-C melanoma pts were included in the phase 1b feasibility OpACIN trial between Augustus 2015 and October 2016. Pts were randomized to receive either IPI 3 mg/kg + NIVO 1 mg/kg 4 cycles adjuvant (adj) after lymph node dissection or split 2 cycles neoadj and 2 adj. The 4-year RFS and OS rates were estimated using the Kaplan Meier method. All comparative efficacy endpoints are descriptive since the trial was not powered for comparison of the arms.
Results
None of the 7 pts with a pathologic response in the neoadj arm have relapsed after a median FU of 48.0 months (minimum 38.1 months FU of pts alive). Within the neoadj arm only the two non-responding pts and the one non-evaluable pt have relapsed, 4 pts have relapsed in the adj arm. Estimated 4-year RFS rate was 60% for the neoadj arm and 60% for the adj arm, the 4-year OS rates were 90% and 70%, respectively. All grade 3-4 immune-related adverse events, initially for both arms reported in 90% of pts, have recovered to grade 1 or less, except for the grade 2 endocrinopathies requiring hormonal replacement therapy that are ongoing within 8 (50%) of the 16 pts alive.
Conclusions
The 4-year survival data of OpACIN indicate that pathologic response upon neoadj IPI + NIVO in macroscopic stage III melanoma is an excellent surrogate marker for long-term outcome (RFS and OS), as none of the responders has relapsed. In combination with data from other neoadj trials, these data suggest that pathologic response could be a valuable outcome parameter in neoadj immune checkpoint inhibitor trials.
Clinical trial identification
NCT02437279.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Bristol-Myers Squibb.
Disclosure
J.V. van Thienen: Advisory/Consultancy, honoraria to institution: Pfizer; Spouse/Financial dependant, other relationship: MSD. J.B.A.G. Haanen: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Neogene Therapeutics; Advisory/Consultancy: Aimm; Advisory/Consultancy: Amgen; Advisory/Consultancy: AZ; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Gadeta; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Immunoscore; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Neon; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Rocher; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics. A.C.J. van Akkooi: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: MSD-Merck; Advisory/Consultancy, Research grant/Funding (institution): Merck-Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: 4SC. T.N. Schumacher: Advisory/Consultancy: Adaptive Biotechnologies; Advisory/Consultancy, Shareholder/Stockholder/Stock options: AIMM Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Allogene Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Merus; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Neon Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Scenic Biotech; Research grant/Funding (institution): Merck KGaA; Shareholder/Stockholder/Stock options: Neogene Therapeutics. C.U. Blank: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): NanoString; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: GSK; Honoraria (institution), Advisory/Consultancy: AZ; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: GenMab; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Third Rock Ventures; Shareholder/Stockholder/Stock options: Uniti Cars; Shareholder/Stockholder/Stock options: Immagene BV. All other authors have declared no conflicts of interest.