503O - Neoadjuvant nivolumab (nivo) plus relatlimab (rela) in MMR-deficient colon cancer: Results of the NICHE-3 study

Background

Immune checkpoint inhibitors (ICI) have shown unprecedented responses in MMR-deficient (dMMR) colorectal cancers. In the NICHE-2 study, major pathologic responses (MPR) and pathologic complete responses (pCR) were observed in 95% and 68% of patients, respectively, following a short neoadjuvant regimen of nivolumab/ipilimumab. Data on nivo/rela in patients with melanoma suggest a favorable toxicity profile. Here we present data from NICHE-3, in which we investigated the efficacy and safety of nivo/rela in locally advanced resectable dMMR colon cancer (CC).

Methods

Patients with dMMR CC were treated with 2 doses of nivo/rela (480mg/480mg) on day 1 and 29, followed by surgery within 8 weeks of enrollment. A Simon’s 2 stage design was used where >46/59 responders were needed in stages 1+2 for the study to be deemed successful. Pathologic response was defined as ≤50% residual viable tumor (RVT). Secondary endpoints included pCR, MPR (≤10% RVT), safety and survival. We previously showed data from stage 1 (19pts). Here we present the primary endpoint from the fully accrued study.

Results

A total of 59 patients were treated. Median age was 65 years and 78% of patients had clinical stage III disease. Of the 59 patients, 56 have undergone surgery, and surgery is scheduled for 3 treated patients. Pathologic response was observed in 54/56 (96%) patients and included 91% MPR and 68% pCR. Grade 3-4 immune related adverse events were observed in 6/59 (10%) patients and led to delay of surgery in 3 patients. Endocrinopathies requiring long-term suppletion occurred in 14 (24%) patients consisting of 10 cases of hypothyroidism (17%) and 5 (8%) of adrenal insufficiency. To date, one patient had recurrence of disease.

Conclusions

Here we present data from NICHE-3 showing that neoadjuvant nivo/rela led to a pathologic response rate of 96% in patients with dMMR CC, with a pCR rate of 68%, similar to response rates observed with nivo/ipi. Toxicity of nivo/rela in this study was manageable but resulted in high rates of long-term endocrinopathies.

This study adds to a growing body of evidence of the role of ICI in dMMR CRC and provides a basis for larger studies and exploration of organ-sparing strategies.

Clinical trial identification

NCT03026140; EudraCT 2016-002940-17.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol Myers Squibb.

Disclosure

P.G.M. de Gooyer: Other, Personal, Partner employed at MSD: MSD. T.N. Schumacher: Financial Interests, Personal, Stocks or ownership, Venture Partner: Third Rock Ventures ; Non-Financial Interests, Personal, Advisory Role: Allogene Therapeutics, Merus, Scenic Biotech, Asher Bio, Cell Control, Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Allogene Therapeutics, Merus, Scenic Biotech ; Financial Interests, Personal, Stocks or ownership, Founder and Stockholder: Asher Bio, Cell Control, Neogene Therapeutics. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Iovance Biotherapeutics, AstraZeneca; 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, Advisory Board: Third Rock Venture, CureVac, Imcyse; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio, Sastra Cell Therapy; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. M. Chalabi: Financial Interests, Institutional, Research Grant: BMS, Roche Genentech, MSD, Agenus; Non-Financial Interests, Advisory Role, Advisory Board: BMS, MSD; Non-Financial Interests, Advisory Role: Kineta. All other authors have declared no conflicts of interest.