High efficacy of pembrolizumab combined with standard therapy in patients with MSS/pMMR mCRC and high immune infiltrate

Presented by

Prof. David Tougeron, Poitiers University Hospital, France

Conference

ESMO GI 2024

Trial

Phase 2, POCHI

Doi
https://doi.org/10.55788/62a51e45

Preliminary results of the phase 2 POCHI trial showed high efficacy of pembrolizumab, combined with standard therapy, in patients with MSS/pMMR metastatic colorectal cancer (mCRC).

In contrast to microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) mCRC, microsatellite stable/proficient mismatch repair (MSS/pMMR) mCRC is currently considered non-responsive to immune checkpoint inhibitors. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour-infiltrating lymphocytes and may therefore be sensitive to immune checkpoint inhibitors.

The multicentre, single-arm, phase 2 POCHI trial (NCT04262687) evaluates the efficacy of the immune checkpoint inhibitor pembrolizumab in combination with CAPOX and bevacizumab as first-line treatment of unresectable MSS/pMMR mCRC in patients with a high immune infiltrate (defined by at least 1 positive immune score [Immunoscore® and/or TuLIS] on primary tumour resection specimens). The primary objective is to increase progression-free survival (PFS) at 10 months from 50% to 70%. The main secondary endpoints are overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety. Prof. David Tougeron (Poitiers University Hospital, France) presented the results of a preliminary analysis [1].

A total of 28 participants with unresectable MSS/pMMR mCRC and at least 1 positive immune score were treated every 3 weeks with a combination of pembrolizumab, CAPOX, and bevacizumab. After a median follow-up of 19 months, 13 participants were still on treatment. A complete response was achieved in 6 participants and a partial response in 15, leading to an ORR of 75%; 6 participants showed stable disease and 1 had disease progression. Median DoR at data cut-off was 10 months (see Figure). Preliminary efficacy data shows a PFS rate at 12 months of 68% and a 24-month OS rate of 67%. Regarding safety, 64% of the participants experienced at least 1 grade 3–4 treatment-related adverse event, but no toxic deaths were observed.

Figure: High overall response with pembrolizumab added to standard therapy in POCHI [1]

CR, complete response, DCR, disease control rate; DoR, duration of response; PD, progressive disease; PR, partial response; SD, stable disease.

“These preliminary results suggest a high efficacy of pembrolizumab combined with standard therapy in patients with MSS/pMMR mCRC and a high immune infiltrate. The observed complete response and disease control rates justify further evaluation of this treatment in a randomised phase 3 trial,” Prof. Tougeron concluded. The trial is still enrolling and biomarker analyses are ongoing.

Tougeron D, et al. 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. Abstract LBA1, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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