Abstract 248P
Background
CA209-8M4 trial is evaluating the addition of nivo to TNT in patients (pts) with LARC. Its preliminary results are presented.
Methods
This is a prospective single arm, phase II study. Pts with LARC (T3-4 N any or T any N1) up to 12 cm from the anal verge received standard chemoradiation (CRT) (50.4Gy with capecitabine 1,650 mg/m2), followed 4 weeks later by chemoimmunotherapy (CIMT): 6 cycles of standard mFOLFOX6 and nivo 240mg, both on day 1, q14 days. We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated pts and long-term (≥12 months) sustained clinical complete response (cCR) rate for those electing watchful waiting over surgery, into a composite endpoint of modified pCR (mpCR) rate. The trial was to be considered positive if the mpCR rate exceeds 40%.
Results
Between 4/2019 - 3/2024, 29 pts were enrolled, median age 53 years (range, 33-81), 21 (72%) males; 90% had T3-4 tumors, and 83% had N+ disease. Median distance from the anal verge was 7cm (range, 0.5-11). MSI status is known in 29 pts, MSS in 28 (96%). At present, 28 pts (96%) initiated CIMT and 25 (86%) have completed it. Eight pts (28%) had grade ≥3 adverse events (AEs) during CIMT, including one fatality (mesenteric inflammation), attributed most likely to CRT's unresolved toxicity. Three pts (11%) experienced immune mediated AEs, grade 1 hepatitis alone (2 pts) or with asymptomatic hyper/hypothyroidism (1). Currently, 20 pts (69%) are evaluable for mpCR: 13 underwent surgery with 6 achieving pCR and 7 were not operated with cCR ≥12 months, leading to a 65% mpCR rate. Three additional unoperated pts are still unevaluable for mpCR due to follow-up <12 months. With a median follow-up of 19.3 months (range, 4.5-59.9), one pt (3%) died of toxicity and 28 pts (97%) are alive: 25 are NED (1 post-metastasectomy) and 3 are still on treatment. More mature data will be presented at the meeting.
Conclusions
The addition of nivo to standard TNT in LARC seems to be safe and may enhance its effectiveness, with an encouraging mpCR rate of 65%. A large multicenter randomized trial, further evaluating this strategy is underway.
Clinical trial identification
NCT03921684.
Legal entity responsible for the study
B. Brenner
Funding
Bristol Myers Squibb.
Disclosure
B. Brenner: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, AbbVie, MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, GSK; Financial Interests, Personal, Research Grant: Merck Serono, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations: Roche, Merck Serono, MSD, Rhenium/Oncotest. G. Perl: Financial Interests, Personal, Advisory Role: Rhenium/Oncotest; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Merck Serono, Rhenium/Oncotest; Financial Interests, Personal, Other, travel & accommodation: Medison, Merck Serono. T. Shalmon: Financial Interests, Personal, Other, Travel, Accommodations: Arcus Biosciences. I. White: Financial Interests, Personal, Stocks/Shares: Moderna; Financial Interests, Personal, Advisory Board: Takeda. Y. Feferman: Financial Interests, Personal, Other, Travel, Accommodations: Dover Medical Ltd. Israel. All other authors have declared no conflicts of interest.