LBA31 - Neoadjuvant nivolumab plus relatlimab (anti-LAG3) in locally advanced MMR-deficient colon cancers: The NICHE-3 study

Background

Neoadjuvant immunotherapy has shown promising responses in various tumor types. In the NICHE-2 study, neoadjuvant nivolumab/ipilimumab in MMR deficient (dMMR) colon cancers resulted in 95% major pathologic responses (MPR), including 67% pathologic complete responses (pCR) within 6 weeks of treatment. In melanoma patients, nivolumab/relatlimab has shown a favorable toxicity profile and promising efficacy in the neoadjuvant setting. We investigated this regimen in patients with non-metastatic dMMR colon cancer (NCT03026140).

Methods

In the NICHE-3 study, patients with resectable, locally advanced (at least cT3 and/or N+), dMMR colon cancer were treated with two doses of nivolumab 480 mg plus relatlimab 480 mg at a 4-week interval, followed by surgery within 8 weeks of registration. Pathologic response was defined as 50% or less residual viable tumor (RVT), and MPR as ≤10% RVT. The primary endpoint was pathologic response rate. According to a Simon-2-stage design, ≥15/19 responders are needed in stage 1 to continue accrual in stage 2. Here we present the prespecified analysis of pathologic response from stage 1.

Results

A total of 19 patients were treated and underwent surgery without delays. Grade 1-2 immune-related adverse events (irAEs) were observed in 14/19 patients (74%), with infusion related reactions being the most frequent (43%). Only one patient (5%) experienced a grade 3 irAE (hyperthyroidisim). Endocrinopathy for which supplementation was required was observed in 4 (21%) patients and consisted of 1 patient with hypothyroidism and 3 patients with hypophysitis with secondary adrenal and/or thyroid insufficiency. There were no grade 4-5 irAEs. With a median of 7.4 weeks between the first dose and surgical resection, the treatment resulted in a 79% pCR rate, 89% MPR rate and 100% overall pathologic response rate among 19 patients.

Conclusions

Here we present data from NICHE-3, the first study showing the safety and efficacy of neoadjuvant nivolumab/relatlimab in dMMR colon cancer patients, with a pathologic response in all patients, including 79% pCR. Accrual is currently ongoing in stage 2, in which an additional 40 patients will be treated.

Clinical trial identification

EudraCT 016-002940-17, NCT03026140.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol Myers Squibb.

Disclosure

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, 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 Sharpe & 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. M. Chalabi: Financial Interests, Institutional, Research Grant: BMS, BMS, Roche Genentech, Roche Genentech; Non-Financial Interests, Advisory Role, Advisory Board: BMS, BMS, MSD. All other authors have declared no conflicts of interest.