Can a Two-Target antibody shrink Hard-to-Treat cancers?

NCT ID NCT03526835

Disease control Sponsor: Merus B.V. Source: ClinicalTrials.gov ↗

First seen Jul 29, 2026 · Last updated Jul 30, 2026 · Updated 1 time

Summary

This trial is testing an experimental drug called petosemtamab (MCLA-158) in people with advanced solid tumors, including colorectal, head and neck, and lung cancers. The drug is a bispecific antibody designed to block two cancer-related proteins, EGFR and LGR5. Researchers want to see if it is safe and effective when used alone or combined with other cancer treatments.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: petosemtamab (MCLA-158), a bispecific antibody targeting EGFR and LGR5, given alone or with pembrolizumab, FOLFIRI, or FOLFOX
What this could lead to: If successful, this could offer a new treatment option for people with advanced solid tumors that have stopped responding to standard therapies.
What could go wrong: This is an early-phase trial, so the drug may not prove effective or may cause significant side effects. Results may not apply to all tumor types.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 560 people

The number the study aims to enrol. It can still change while the study runs.

Started

May 2018

Expected to finish

Nov 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent. * A baseline fresh tumor sample (FFPE) from a metastatic or primary site (if safe/feasible). * Amenable for biopsy (if safe/feasible). * Measurable disease as defined by RECIST version 1.1 by radiologic methods. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy ≥ 12 weeks, as per investigator. * Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA). * Adequate organ function * Expansion cohorts: patients with locally advanced unresectable or metastatic disease for the following indications: SINGLE AGENT: * SECOND-/THIRD-LINE HNSCC PATIENTS (cohort closed to enrolment): patients who have progressed on or after, or are intolerant to, anti-PD-(L)1 therapy and platinum therapy as monotherapy or in combination with other agents and no previous exposure to EGFR inhibitors. Patients treated with platinum-containing therapy only in the adjuvant setting, or in the context of multimodal therapy for locally advanced disease should have disease progression within 6 months of the last dose of platinum containing therapy. Patients with no more than 2 prior lines of treatment in recurrent or metastatic disease. • Human papilloma virus (HPV) status determined by p16 immunohistochemistry (IHC) or molecular HPV test for all oropharyngeal tumors should be reported when available. * The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * 3L+ mCRC (cohort open to enrolment) patients must have: * No oncogenic missense mutations in KRAS, NRAS, BRAF, or EGFR ectodomain, and no HER2 (ERBB2) or KRAS amplification, as detected in plasma by ctDNA NGS central testing performed during screening. * A microsatellite stable (MSS) tumor. * Received ≥2 and no more than 4 lines of prior therapy in the metastatic setting including: 1. Chemotherapy with oxaliplatin, irinotecan, and a fluoropyrimidine, 2. Targeted therapy with an anti-VEGF therapy COMBINATION: * FIRST-LINE HNSCC (cohort closed to enrolment): patients eligible to receive pembrolizumab as first-line monotherapy with tumors expressing programmed cell death protein ligand 1 (PD-L1), combined positive score (CPS) ≥1, as determined by a Food and Drug Administration (FDA) approved test in the US, or by an approved equivalent test in other countries; patients should not have previous systemic therapy administered in the recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is allowed if ended ≥6 months prior to signing the ICF. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Previous treatments with anti PD-(L)1 or anti-EGFR therapies are not allowed. * mCRC (cohorts open to enrolment): Patients should have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. Patients must be RAS/ RAF WT as determined using tumor tissue (primary or metastatic) by an appropriate tumor tissue based assay, to be confirmed by the sponsor, and must have an MSS tumor. Patients must be naive to prior anti-EGFR therapy. i. Cohort to be treated with petosemtamab and FOLFIRI: patients may have received up to 1 prior chemotherapy regimen for the metastatic setting, consisting of 1L fluoropyrimidine-oxaliplatin-based chemotherapy ± bevacizumab. ii. Cohort to be treated with petosemtamab and FOLFOX: patients may have received up to 1 prior chemotherapy regimen in the metastatic setting consisting of 1L fluoropyrimidine-irinotecan-based chemotherapy ± bevacizumab Exclusion Criteria: * Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry. * Known leptomeningeal involvement. * Participation in another clinical study or treatment with any investigational drug within 4 weeks prior to study entry. * Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is shorter of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout period of 6 weeks is required. * Requirement for immunosuppressive medication (e.g. methotrexate, cyclophosphamide) * Major surgery or radiotherapy within 3 weeks of the first dose of study treatment. Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible, irrespective of when it was received. * Persistent grade \>1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 NCI-CTCAE v4.03 is allowed. * History of hypersensitivity reaction to any of the excipients of petosemtamab, human proteins or any non-IMP treatment required for this study. * Uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mmHg and/or diastolic BP \> 100 mmHg) with appropriate treatment or unstable angina. History of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia). History of myocardial infarction within 6 months of study entry. * History of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease for 3 years. * Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy. Patients with a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of ILD on baseline chest computerized tomography (CT) scan. * Current serious illness or medical conditions including, but not limited to uncontrolled active infection,clinically significant pulmonary, metabolic or psychiatric disorders. * Patients with known infectious diseases: i. Active hepatitis B infection (hepatitis B surface antigen \[HBsAg\] positive) without receiving antiviral treatment. ii. Positive test for hepatitis C ribonucleic acid (HCV) RNA). • Pregnant or breastfeeding patients; patients of childbearing potential must use highly effective contraception methods prior to study entry, for the duration of study participation, and for 6 months after the last dose of MCLA-158.

Get updates

Get notified about this study

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

carcinoma of esophagus colorectal cancer colorectal neoplasm esophageal cancer Esophageal Neoplasms gastric cancer gastric neoplasm gastroesophageal cancer gastroesophageal junction adenocarcinoma head and neck squamous cell carcinoma metastatic malignant neoplasm non-small cell lung carcinoma pancreatic adenocarcinoma Squamous Cell Carcinoma of Head and Neck

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced/metastatic solid tumors Colorectal cancer Esophageal cancer Gastric cancer Gastroesophageal junction cancer Head and neck squamous cell carcinoma HNSCC NSCLC

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

47 sites in 7 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

ASST Grande Ospedale Metropolitano Niguarda
RECRUITING

Milan, 20162, Italy
Cambridge University Hospitals NHS Foundation Trust
COMPLETED

Cambridge, United Kingdom
Cancer Care Northwest
RECRUITING

Spokane, Washington, 99202, United States
Cayuga Medical Center
RECRUITING

Ithaca, New York, 14850, United States
Centre Antoine Lacassagne
RECRUITING

Nice, France
Centre Henri Becquerel
RECRUITING

Rouen, France
Centre Leon Berard
RECRUITING

Lyon, France
Chu Ucl Namur Site De Sainte-Elisabeth
RECRUITING

Namur, Belgium
Cleveland Clinic
RECRUITING

Cleveland, Ohio, 44195, United States
Clinica Universidad de Navarra
RECRUITING

Pamplona, Spain
Cliniques universitaires Saint-Luc
RECRUITING

Brussels, Belgium
Emory University
RECRUITING

Atlanta, Georgia, 30322, United States
Florida Cancer Specialists
ACTIVE_NOT_RECRUITING

Fort Myers, Florida, 33901, United States
Georgetown University Medical Center
RECRUITING

Georgetown, Washington, 20007, United States
Hematology-Oncology Associates of Central New York
RECRUITING

Syracuse, New York, 13057, United States
Hopital La Timone
RECRUITING

Marseille, France
Hopital Saint Andre, CHU Bordeaux
RECRUITING

Bordeaux, France
Hospital 12 de Octubre
RECRUITING

Madrid, Spain
Hospital Universitario de Navarra
RECRUITING

Pamplona, Spain
Institut Curie
RECRUITING

Paris, France
Institut Gustave Roussy
RECRUITING

Paris, France
Institut Jules Bordet
COMPLETED

Brussels, Belgium
Institut Régional du Cancer de Montpellier
RECRUITING

Montpellier, France
Instituto Valenciano de Oncologia
RECRUITING

Valencia, Spain
Karmanos Cancer Institute
COMPLETED

Detroit, Michigan, 48201, United States
Massachusetts General Hospital - Dana Farber
RECRUITING

Boston, Massachusetts, 02114, United States
Memorial Sloan Kettering Cancer Center
RECRUITING

New York, New York, 10065, United States
Mt. Sinai
RECRUITING

New York, New York, 10029, United States
NKI - Antoni van Leeuwenhoek
RECRUITING

Amsterdam, Netherlands
Ohio State University
RECRUITING

Columbus, Ohio, 43221, United States
Oncology & Hematology Associates of Southwest Virginia
RECRUITING

Roanoke, Virginia, 24014, United States
Oncology Consultants
RECRUITING

Houston, Texas, 77030, United States
Rocky Mountain Cancer Centers
RECRUITING

Lone Tree, Colorado, 80124, United States
SSM Health Saint Louis University Hospital
COMPLETED

St Louis, Missouri, 63110, United States
SSM OKC Hightower Clinical
RECRUITING

Oklahoma City, Oklahoma, 73102, United States
Sarah Cannon Research Institute
COMPLETED

Nashville, Tennessee, 37203, United States
Sarah Cannon Research Institute
RECRUITING

London, United Kingdom
Sarah Cannon Research Institute (Lake Nona)
RECRUITING

Orlando, Florida, 32827, United States
Sharp Healthcare
RECRUITING

San Diego, California, 92123, United States
Taylor Cancer Research Center
RECRUITING

Maumee, Ohio, 43537, United States
Texas Oncology
RECRUITING

Dallas, Texas, 75246, United States
Texas Oncology
RECRUITING

Tyler, Texas, 75702, United States
The University Of Tennessee Health Science Center
RECRUITING

Memphis, Tennessee, 38103, United States
UCSD
RECRUITING

La Jolla, California, 92093, United States
UMC Radboud
RECRUITING

Nijmegen, Netherlands
UMC Utrecht
RECRUITING

Utrecht, Netherlands
USC Norris Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING

Los Angeles, California, 90033, United States
UZ Gent
RECRUITING

Ghent, Belgium
University of Florida
RECRUITING

Gainesville, Florida, 32610, United States
University of Pennsylvania
RECRUITING

Philadelphia, Pennsylvania, 19104, United States
University of Utah Health Huntsman Cancer Hospital
RECRUITING

Salt Lake City, Utah, 84112, United States
Utah Cancer Specialists
RECRUITING

Salt Lake City, Utah, 84106, United States
Vall d'Hebron
RECRUITING

Barcelona, Spain
Washington University School of Medicine at St Louis
RECRUITING

St Louis, Missouri, 63110, United States

More trials for these conditions

Other studies related to the condition(s) this trial covers.