504O - IMHOTEP Phase II trial of neoadjuvant pembrolizumab in dMMR/MSI tumors: Results of the colorectal cancer cohort

Background

Pembrolizumab (P) is approved in metastatic dMMR/MSI (deficient mismatch repair/microsatellite instability) colorectal cancer (CRC). Neoadjuvant immunotherapy has also shown promising preliminary results in early stages.

Methods

IMHOTEP is a multicenter, single-arm study evaluating peri-operative P in 4 different cohorts of patients (pts) with localized resectable dMMR/MSI tumors. Pts received P (400 mg IV, Q6W) in the neoadjuvant (1 or 2 cycles (cy)) and adjuvant setting for a total of 1 year. Primary endpoint is complete pathological response (pCR) rate defined as ypT0N0. Using a Bayesian design, the study was considered as positive if the probability that pCR rate >= 50% was high. Here are the results of the CRC cohort.

Results

87 CRC pts were included (72 colon; 15 rectum). Median age was 66 years (21-89) and 20.7% had Lynch syndrome. Surgery was performed in 76 pts (65 colon, 11 rectum) including 51 (67.1%) and 25 (32.9%) after 1 and 2 P cy, respectively. pCR was obtained in 41 pts (53.8%, 95% CI [42.8%; 64.7%]), including 36 (55.4%) colon and 5 (45.5%) rectal cancers. ypTNM stage is reported in the table. pCR rate increased with the number of P cy from 47.1% with 1 to 68.0% with 2 P cy. A multivariate logistic model showed an association between the number of P cy and the pCR rate increase (OR: 3.6, 95% CI [1.2; 11.3], p=.026). 11 pts were not submitted to surgery and received a median number of 5 P cy (1 to 9). Among them, only one was not operated because of disease progression. Treatment-related adverse-events grade >=3 were observed in 8 pts (9.2%). Table: 504O

Conclusions

The IMHOTEP trial met its primary endpoint in dMMR/MSI localized resectable CRC pts demonstrating P efficacy as a neoadjuvant monotherapy. This is the first study showing that pCR rate increases with the number of neoadjuvant P cycles, questioning the optimal number of cycles in this setting.

Clinical trial identification

NCT04795661 - 11 March 2021; EudraCT 2020-004957-62.

Editorial acknowledgement

Legal entity responsible for the study

Centre Leon Berard.

Funding

French Ministry of Health: PHRC_2019 INCa-DGOS_14333.

Disclosure

C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol-Myers Squibb, Incyte, Daiichi Sankyo, Astellas; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daichi Sankyo, MSD. R. Cohen: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Exeliom Biosciences, Enterome Biosciences; Financial Interests, Personal, Invited Speaker: Pierre Fabre, MSD Oncology, Servier, AstraZeneca; Financial Interests, Personal, Research Grant: Servier Institute. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. E. Soularue: Financial Interests, Personal, Advisory Board: Amgen; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Prodige. O. Dubreuil: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Sanofi, Pierre Fabre, Servier, MSD, AstraZeneca. V. Hautefeuille: Financial Interests, Personal, Invited Speaker: Novartis, Merck, Amgen; Financial Interests, Personal, Advisory Board: AAA, IPSEN, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Deciphera, Esteve. M. Jary: Financial Interests, Personal, Invited Speaker: Pierre Fabre, Servier, MSD, BMS, Amgen; Financial Interests, Personal, Writing Engagement: Incyte; Other, participation to congresses: Pierre Fabre, Roche, Bayer, Servier, MSD, BMS. M. Ben Abdelghani: Financial Interests, Personal, Invited Speaker: Incyte, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck, BMS, Bayer; Financial Interests, Institutional, Advisory Board: Deciphera. L. Evesque: Financial Interests, Personal, Advisory Board: Servier, Amgen, MSD, Merck, Astellas. F. Bibeau: Financial Interests, Personal, Advisory Board: Astellas, Sanofi, Pierre Fabre, GSK; Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca, Pierre Fabre, Incyte, Servier; Financial Interests, Institutional, Funding: BMS, Sanofi. C. Coutzac: Financial Interests, Personal, Advisory Board: BMS, Servier, Pierre Fabre, Merck Serono; Financial Interests, Institutional, Advisory Board: BMS, Amgen; Financial Interests, Institutional, Invited Speaker: Daiichy Sankyo, AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: ImCore Roche Genetech. All other authors have declared no conflicts of interest.