LBA1 - Pembrolizumab in combination with xelox and bevacizumab in patients with microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC) and a high immune infiltrate: A proof of concept study - Preliminary results of FFCD 1703 POCHI trial

Background

Immune checkpoint inhibitors (ICI) are currently considered ineffective in pMMR/MSS mCRC. However, about 15% of pMMR/MSS CRCs are highly infiltrated by tumor infiltrating lymphocytes and may be sensitive to ICIs. Some immune scores based on CD3+ and/or CD8+ T-cells infiltration are validated to assess lymphocyte infiltration in CRCs.

Methods

POCHI is a multicentre, single-arm phase II trial aiming to evaluate efficacy of Pembrolizumab (anti-PD1) in combination with CAPOX and bevacizumab as first-line treatment of unresectable pMMR/MSS mCRC patients (pts) with a high immune infiltrate defined by at least one positive immune score (Immunoscore® and/or TuLIS) on primary tumor resection specimens. Primary objective was to increase progression-free survival (PFS) at 10 months from 50% to 70%. Main secondary objectives were overall survival, disease control rate (DCR), safety and duration of response (DoR). With a one-sided type one error α of 5%, a power of 85%, 55 pts were required.

Results

Between April 2021 and May 2024, 182 pts were screened in 40 active centres and 28 had at least one positive immune score (15%) and were included in the POCHI trial. Median age was 66 years, 61% were men and 86/14% were ECOG PS 0/1. Most pts had right-sided primary tumour (43%), RAS-mutated tumour (65%) and lung (29%) and liver metastases (46%). At the time of this preliminary analysis (cut-off date May 27, 2024), median follow-up was 19 months and 13/28 pts (46%) were still on treatment. Complete response (21%), partial response (54%) or stable disease (21%) led to a DCR of 96%. Median DoR was 10 months. 25/28 pts were still alive and 12-month PFS was 68%. At least one grade 3-4 treatment related adverse event was observed in 64% of pts. No toxic death was observed.

Conclusions

These preliminary results of the POCHI trial demonstrate a good safety profile and a high efficacy of Pembrolizumab combined to a standard therapeutic regimen. The impressive CR rate and DCR observed justify further evaluation of the quadruplet treatment combination in a randomized phase III trial dedicated pMMR/MSS mCRC pts with a high immune infiltrate.

Clinical trial identification

NCT04262687.

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

Fédération Francophone de Cancérologie Digestive, MSD and Veracyte.

Disclosure

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: Fédération Francophone de Cancérologie Digestive. B. Chibaudel: Financial Interests, Personal, Expert Testimony: Amgen, Beigene, Biocartis, Lilly, Merck, MSD, Pfizer, Pierre Fabre, Roche, SeqOne, Sanofi, Servier, Takeda; Financial Interests, Personal, Advisory Board: Bayer. A. Lievre: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, BMS, Esteve, Pierre Fabre Oncologie, Servier, Viatris; Financial Interests, Personal, Advisory Board: Astellas, BMS, Bayer, Servier; Financial Interests, Institutional, Research Grant, RePERSO trial: Bayer; Financial Interests, Institutional, Invited Speaker, SOCRATE trial (FFCD promotion): Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Bayer, Incyte, Lilly; Non-Financial Interests, Other, Travel and meeting registration: Bayer, Pierre Fabre, Servier, Viatris. C. Toullec: Financial Interests, Personal, Invited Speaker: Amgen, BMS, MSD, Pierre Fabre, Viatris; Financial Interests, Personal, Advisory Board: Bayer, Sanofi, Servier, AstraZeneca, Oncoscience; Financial Interests, Personal, Expert Testimony: Merck Serono. M. Muller: Financial Interests, Institutional, Invited Speaker: Servier. P. Laurent-Puig: Financial Interests, Personal, Invited Speaker: Amgen, Sanofi; Financial Interests, Personal, Advisory Board: Biocartis, Pierre Fabre; Financial Interests, Personal, Ownership Interest: Methys DX; Financial Interests, Institutional, Research Grant, PI of translational research: Fédération Francophone de Cancérologie Digestive; Non-Financial Interests, Leadership Role: President of Canceropole Ile de France. C. Lepage: Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Invited Speaker: Amgen, Pierre Fabre, Ipsen. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Expert Testimony: Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, Steering Committee of clinical trial: Novartis; Non-Financial Interests, Leadership Role, President of the Scientific Committee until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD Pancreas Research Group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships/partnership for FFCD in the Prodige Intergroup: Fédération Francophone de Cancérologie Digestive (FFCD); Non-Financial Interests, Other, steering committee of clinical trials: Pfizer, Servier. All other authors have declared no conflicts of interest.