573P - M9140, an anti-CEACAM5 antibody drug conjugate (ADC), in patients with metastatic colorectal cancer (mCRC): Updated results from a phase I trial

Background

M9140 is an anti-CEACAM5 ADC that selectively delivers a cytotoxic topoisomerase 1 inhibitor payload (exatecan). Preliminary data from the dose escalation part of the ongoing trial (NCT05464030) showed encouraging antitumor activity and a manageable safety profile of M9140 in heavily pretreated patients with mCRC. Herein, longer follow-up data and biomarker analysis will be presented.

Methods

Part 1 of this Phase 1 trial investigated the safety and preliminary clinical activity of M9140 monotherapy (Q3W; IV) in patients with 3L+ mCRC. In addition to CEACAM5 IHC from archival tissue, patient records/archival tissue were assessed for KRAS, NRAS, and BRAF mutations.

Results

As of April 2024, 40 patients were treated across 7 dose levels (DLs) (0.6–3.2 mg/kg; 3 patients with primary G-CSF prophylaxis at DL 3.2 mg/kg). Median treatment duration was 16.4 weeks (range: 1.7–47). Overall, 4 (10%) patients achieved partial response (PR; including 1 unconfirmed PR) at DLs ≥2.4 mg/kg, and 0 at <2.4 mg/kg. Stable disease was observed in 22 (55.0%) patients, progressive disease in 7 (17.5%) patients, and the best overall response was not evaluable in 7 (17.5%) patients. Progression-free survival was higher for patients treated with M9140 ≥2.4 mg/kg vs <2.4 mg/kg (6.7 [95% CI 5.0, 8.8] vs 2.1 [95% CI 1.2, ne] months). Eleven (27.5%) patients continue on treatment. Overall, 7 patients experienced dose-limiting toxicities; the majority were hematological adverse events at DLs 3.0 and 3.2 mg/kg (most self-resolved); 1 patient (at 2.8 mg/kg) had a Grade 5 sepsis. No events of interstitial lung disease or ocular toxicity were observed. Updated data with a longer follow-up (data cutoff: early August) will be presented at the congress. The association of M9140 activity with KRAS, NRAS, BRAF mutation status and CEACAM5 levels will also be presented.

Conclusions

With continued follow-up, M9140 continues to exhibit a manageable and predictable safety profile. Encouraging antitumor activity was observed at DLs ≥2.4 mg/kg. DLs 2.4 and 2.8 mg/kg, identified as the recommended doses for expansion, are currently being evaluated in the randomized dose optimization part of the study.

Clinical trial identification

NCT05464030.

Editorial acknowledgement

Medical writing assistance was provided by Gaurav Vijay Jadhav of Merck Specialities Pvt. Ltd, Bangalore, India, an affiliate of Merck KGaA.

Legal entity responsible for the study

Merck.

Funding

The study was sponsored by Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

V. Boni: Financial Interests, Institutional, Full or part-time Employment: Quironsalud, Next Oncology; Financial Interests, Institutional, Stocks or ownership: 1TRIALSP; Financial Interests, Institutional, Royalties: Loxo, IDEAYA Biosciences, Puma Biotechnology, Amunix, Guidepoint Global, MSD Oncology, Janssen Oncology, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; Financial Interests, Institutional, Advisory Role: OncoArt, Guidepoint Global, Janssen Research & Development, Lilly, Nanobiotix, Novartis, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; Financial Interests, Institutional, Research Funding: Sanofi, Seagen, Loxo, Novartis, CytomX Therapeutics, Puma Biotechnology, Kura Oncology, Tesaro, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck Healthcare KGaA, Darmstadt, Germany, Lilly, Merus, Pfizer, Bayer, Incyte, Abb; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: START, Bayer; Financial Interests, Institutional, Speaker’s Bureau: Solti, Lilly, TACTICS, MSD, TACTICS;. S. Kopetz: Financial Interests, Institutional, Advisory Role: Genentech, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, MSD, Holy Stone Healthcare, Novartis, Lilly, AstraZeneca/MedImmune, Bayer Health, Redx Pharma, Ipsen, HalioDx, Lutris, Jacobio, Pfizer, Repare Th; Financial Interests, Institutional, Stocks or ownership: Lutris, Iylon, Frontier Medicines, Xilis, and Navire; Financial Interests, Institutional, Research Funding: Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, MedImmune, Novartis, Amgen, Lilly, and Daiichi Sankyo. K. Kato: Financial Interests, Institutional, Advisory Role: Ono Pharmaceutical, BeiGene, MSD, Oncolys BioPharma, Bayer; Financial Interests, Institutional, Royalties: Lilly, Bristol-Myers Squibb, Ono Pharmaceutical; Financial Interests, Institutional, Research Funding: Ono Pharmaceutical, Shionogi, MSD Oncology, BeiGene, Chugai Pharma, Bayer, AstraZeneca, Taiho Pharmaceutical; Financial Interests, Institutional, Speaker’s Bureau: Ono Pharmaceutical, Bristol-Myers Squibb Japan, MSD. K. Raghav: Financial Interests, Institutional, Advisory Role: Bayer, Eisai, MSD, Daiichi Sankyo, AstraZeneca, Seagen; Financial Interests, Institutional, Royalties: Bayer, Eisai, MSD, Daiichi Sankyo, AstraZeneca, Seagen; Financial Interests, Institutional, Research Funding: Bayer, Roche/Genentech, Guardant Health, HiberCell, Merck Healthcare KGaA, Darmstadt, Germany, Abbvie, Eisai, Xencor, Innovent Biologics, Janssen, UCB, Daiichi Sankyo, AstraZeneca. M. Vieito: Financial Interests, Personal, Invited Speaker: NOVOCURE; Financial Interests, Personal, Other, Steering committee member: BMS; Non-Financial Interests, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. A.G. Pallis: Financial Interests, Institutional, Full or part-time Employment: Merck Santé S.A.S., Lyon, France, an affiliate of Merck KGaA. C. Habermehl: Financial Interests, Institutional, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. I.I. Rodriguez Rivera: Financial Interests, Institutional, Full or part-time Employment: Next Oncology, Texas Oncology; Consulting and advisory role: Syneos Health, Cardinal Health, Werewolf Therapeutics, Telix Pharmaceuticals; Financial Interests, Institutional, Research Funding: 1st Biotherapeutics, Amgen, Apollo Therapeutics, BeiGene, Boundless Bio, Deciphera Pharmaceuticals, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Flare Therapeutics, Kumquat Biosciences Inc, Navire Phar.