1448P - IMHOTEP phase II trial of neoadjuvant pembrolizumab in dMMR/MSI localized cancers: Results of the digestive non-colorectal cancer cohorts

Background

Pembrolizumab (P), a programmed death 1 (PD-1) inhibitor, has been approved in pretreated, unresectable or metastatic dMMR/MSI (deficient mismatch repair/microsatellite instability) cancers. In localized non-colorectal (CRC) dMMR/MSI cancer patients, neoadjuvant immunotherapy has shown interesting preliminary results.

Methods

IMHOTEP is a multicentre, single-arm phase II study evaluating neoadjuvant P in 4 different cohorts of patients (pts) with localized resectable dMMR/MSI or EBV+ tumors. Pts received 400 mg IV of P Q6W for 1 or 2 cycles before surgery and thereafter for a total of one-year treatment. Primary endpoint is the 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 2 digestive non-CRC cohorts.

Results

39 oesophago-gastric cancer (OGC) (5 oesophagus, 11 cardia, 23 gastric including 1 EBV+) and 16 miscellaneous digestive cancers (MDC) pts (14 small intestine, 1 ampullary, 1 biliary-tract) were enrolled. Median age was 74.0 (53-88) and 62.5 (38-81) in both cohorts, respectively. Surgery was performed in 29 (74.4%) OGC and 12 (75%) MDC pts, after 1 (14 OGC; 3 MDC) or 2 P (15 OGC, 9 MDC) cycles. The pCR rates were 5/29 (19.4%, 95%CI [7.7; 34.7%]) and 8/12 (64.3%, 95%CI [38.6; 86.1%]) in OGC and MDC cohort, respectively. In both cohorts, P cycles number did not influence significantly the pCR rate. In the 14 pts who did not undergo surgery, the median number of cycles of P was 3 (1-10) in OGC and 7 (7-10) in MDC cohort. Eight pts decided to not be operated (5 OGC, 3 MDC), 2 had disease progression (2 OGC), 2 had treatment-related adverse events (TRAE) before surgery (1 OGC, 1 MDC) and 2 pts were not operated due to investigator decision (1 OGC, 1 MDC). Grade >=3 TRAE were observed in 4 OGC pts (10.2%), 0 in the MDC pts.

Conclusions

P demonstrated significant efficacy as neoadjuvant therapy in dMMR/MSI miscellaneous digestive cancer pts (mainly small-intestine tumors) but, in OGC, results were not considered positive. Further ancillary analyses and pathological review are ongoing and will provide additional information.

Clinical trial identification

NCT04795661 - 11 March 2021, EudraCT: 2020-004957-62.

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Bérard.

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, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daiichi 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; Other, Participation to congresses: Roche, Bayer; Other, Participation to Congress: 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: Daiichi Sankyo, AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: ImCore Roche Genentech. All other authors have declared no conflicts of interest.