Merus’ Interim Data on Petosemtamab in Metastatic Colorectal Cancer Demonstrates Monotherapy Activity and Robust Response Rate in Combination with FOLFOX/FOLFIRI with Well Tolerated Safety

Rhea-AI Summary

Merus (Nasdaq: MRUS) reported interim phase 2 data for petosemtamab (MCLA-158) in metastatic colorectal cancer as of a July 29, 2025 cutoff.

Key findings: 54 patients treated (1L/2L with FOLFOX/FOLFIRI or 3L+ monotherapy); 1L left-sided showed a 100% response rate (8/8) (confirmed+unconfirmed), 1L overall ~90% (9/10) post-cutoff; 2L response rate 62% (8/13); 3L+ monotherapy confirmed response 10% (2/20) efficacy-evaluable. Safety: no new safety signals and manageable infusion reactions; no discontinuations due to IRRs.

Positive

• 1L left-sided response 100% (8/8, confirmed+unconfirmed)
• 1L overall ~90% (9/10) after post-cutoff confirmation
• 2L response rate 62% (8/13 efficacy-evaluable)
• No new safety signals identified in mCRC combinations

Negative

• 3L+ confirmed response 10% (2/20 efficacy-evaluable)
• Small efficacy cohorts (1L n=10 evaluable, 2L n=13, 3L+ n=20)
• Many responses unconfirmed at data cutoff and pending confirmation

Insights

Clinical Oncology Expert

Interim phase 2 mCRC data show high response rates in small 1L left-sided cohort and activity with FOLFOX/FOLFIRI; results are early.

Petosemtamab (MCLA-158) shows notable tumor shrinkage when combined with standard chemotherapy: a reported 100% response rate in 1L left-sided mCRC (n=8, confirmed and unconfirmed) and a 62% response rate in 2L (n=13, confirmed and unconfirmed). The monotherapy cohort in later lines showed limited confirmed responses (10%). Safety appears manageable with no new signals and no overlapping toxicities reported with FOLFOX/FOLFIRI.

The business mechanism is straightforward: pairing a bispecific targeting EGFR and LGR5 with backbone chemotherapy aims to deepen responses in EGFR inhibitor‑naïve, RAS/BRAF wildtype, microsatellite stable mCRC. Key dependencies include small cohort sizes, reliance on unconfirmed responses that were later partly confirmed, and the limited follow‑up inherent to an interim cut (July 29, 2025). Watch for confirmation of unconfirmed responses in longer follow‑up, durability data and objective response confirmation in larger cohorts presented at the plenary on October 24, 2025; these items will materially affect interpretation over the next 3–12 months.

– 100% response rate in 1L left-sided mCRC (n=8, confirmed and unconfirmed)

– 62% response rate in 2L left- and right-sided mCRC (n=13, confirmed and unconfirmed) 

UTRECHT, The Netherlands and CAMBRIDGE, Mass., Oct. 24, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics^®, Triclonics^® and ADClonics^®), today announced interim clinical data as of a July 29, 2025 data cutoff from the ongoing phase 2 trial of the bispecific antibody petosemtamab in combination with standard of care FOLFOX/FOLFIRI in 1L and 2L metastatic colorectal cancer (mCRC), and petosemtamab monotherapy in 3L+ mCRC. These data will be presented in a plenary session oral presentation by Dr. Moh’d Khushman M.D., Washington University School of Medicine, St. Louis, MO, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Friday, October 24 at 10:20 a.m. ET.

“Petosemtamab’s unique mechanism of action, including targeting both EGFR and LGR5, and potential to safely combine with FOLFOX/FOLFIRI, represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer,” said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. “These data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma. We are encouraged that petosemtamab has the potential to become a transformational treatment and new standard of care for patients across a range of solid tumors.”

“Metastatic colorectal cancer remains a formidable challenge with limited effective therapies. The promising early results with petosemtamab offer hope for advancing care and bringing new treatment possibilities to patients facing this difficult disease,” added Dr. Khushman.

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics^®)

Presentation title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial
Observations in the presentation include:
As of a July 29, 2025 data cutoff date:  

• 54 patients (pts) with left- and/or right-sided, KRAS, NRAS, and BRAF wildtype microsatellite stable mCRC received petosemtamab 1500 mg every two weeks, in combination with FOLFOX/FOLFIRI or as monotherapy
  • Pts treated in 1L or 2L had no prior anti-EGFR therapy
  • Pts treated in 2L received 1 prior chemotherapy regimen in the metastatic setting
  • Pts treated in 3L+ received at least 2 prior regimens in the metastatic setting, including a prior anti-EGFR therapy
• Efficacy evaluable population consisted of patients with ≥1 dose of petosemtamab who had opportunity for ≥8 weeks follow up and ≥1 post baseline tumor assessment or discontinued petosemtamab early due to disease progression, symptomatic deterioration and/or death
• 1L petosemtamab with FOLFOX/FOLFIRI
  • 14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI)
  • 10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment
  • 80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs)
  • 88% (7 of 8) response rate in left-sided: 1 confirmed complete response, 6 PRs (3 unconfirmed, 1 unconfirmed response confirmed post data cutoff); 1 SD
  • One SD observed to be an unconfirmed PR post data cutoff leading to 100% (8/8) response rate left-sided and 90% (9/10) response rate overall in 1L
  • All unconfirmed PRs remained on treatment without disease progression
• 2L petosemtamab with FOLFOX/FOLFIRI
  • 14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI)
  • 13 were efficacy evaluable; 10 (77%) remained on treatment
  • 62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan
  • All unconfirmed PRs and SDs remained on treatment without disease progression
• 3L+ petosemtamab monotherapy:
  • 26 pts were treated
  • 20 were efficacy evaluable, 6 (30%) remained on treatment
  • 10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment)
• Safety:
  • Petosemtamab safety profile in mCRC observed thus far, appears consistent with its established safety profile in recurrent/metastatic head and neck squamous cell carcinoma
  • No significant overlapping toxicities identified in combination with FOLFOX/FOLFIRI
  • No new safety signals identified
  • Infusion related reactions (IRRs) were managed with premedication and prolonged infusion on cycle 1 day 1; no discontinuations due to IRRs

Presentation: 
Title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial 
Session Title: Plenary Session 4: Clinical Trials Plenary Session 
Date and Time: Friday, October 24, 10:20 a.m. ET 
The same data will also be available in a poster: 
Session Title: Poster Session B 
Session Date and Time: Friday, October 24, 12:30-4:00 p.m. ET 

As full presentations become available at the conference, they will contemporaneously be available on the Merus website.

About Merus N.V.  
Merus is an oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics^®. Multiclonics^® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding our belief that petosemtamab’s unique mechanism of action including targeting both EGFR and LGR5, and its potential ability to safely combine with FOLFOX/FOLFIRI represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer; our belief that these data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma; the potential for petosemtamab to become a transformational treatment and new standard of care for patients across a range of solid tumors; the promise of early results with petosemtamab to offer hope for advancing care and bringing new treatment possibilities to patients having mCRC; the potential further investigation of petosemtamab in patients with mCRC; the clinical development of our clinical candidates, including petosemtamab, future clinical trial results or interim data, clinical activity and safety profile, and development plans in the on-going trials and described in forthcoming posters or presentations. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics^® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.

These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended June 30, 2025, filed with the Securities and Exchange Commission, or SEC, on August 5, 2025, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Multiclonics^®, Biclonics^®, Triclonics^®, and ADClonics^® are registered trademarks of Merus N.V.

Investor and Media Inquiries:  
Sherri Spear 
Merus N.V. 
SVP Investor Relations and Strategic Communications
617-821-3246 
s.spear@merus.nl

Kathleen Farren  
Merus N.V. 
Director Investor Relations and Corporate Communications 
617-230-4165 
k.farren@merus.nl

FAQ

What response rates did MRUS report for petosemtamab in 1L metastatic colorectal cancer?

MRUS reported a 100% response rate in 1L left-sided mCRC (8/8 confirmed+unconfirmed) and ~90% overall in 1L after a post-cutoff confirmation (9/10).

What was the response rate for petosemtamab plus FOLFOX/FOLFIRI in 2L mCRC (MRUS)?

The 2L efficacy-evaluable population showed a 62% response rate (8 partial responses of 13 evaluable patients).

How many patients were treated with petosemtamab in the phase 2 mCRC study (MRUS) as of July 29, 2025?

A total of 54 patients received petosemtamab 1500 mg every two weeks across 1L, 2L (with FOLFOX/FOLFIRI) and 3L+ monotherapy.

What were the safety findings for petosemtamab in MRUS's mCRC data?

No new safety signals were identified; infusion-related reactions were managed with premedication and prolonged infusion, with no discontinuations due to IRRs.

What efficacy was seen for petosemtamab monotherapy in 3L+ mCRC in MRUS data?

In 3L+ monotherapy, the efficacy-evaluable group (20 patients) had a 10% confirmed response rate (2 partial responses) and 9 stable diseases.

When and where will Merus present the petosemtamab mCRC data (MRUS)?

The data were presented in a plenary oral presentation on October 24, 2025 at 10:20 a.m. ET at the AACR-NCI-EORTC conference, with a poster session later that day.