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A Study of MCLA-158 for Advanced Solid Tumors

This study is testing MCLA-158, a bispecific antibody, alone or in combination with other treatments for advanced solid tumors like colorectal, gastric, gastroesophageal-junction, and non-small cell lung cancer (NSCLC). Researchers want to see how safe MCLA-158 is and if it helps shrink tumors. You might be eligible if you have advanced cancer that hasn't responded to standard treatments and are at least 18 years old. The study is looking for side effects (toxicities) and how well patients tolerate the treatment. The initial dose-finding part of the study is complete, and they are now exploring MCLA-158 in different cancer types and combinations.

Study design
This is an open-label, multi-center study with an estimated enrollment of 523 participants. It has two parts: a completed dose escalation phase and an ongoing expansion phase.
What's involved
You would need to provide a fresh tumor sample and be able to have a biopsy if needed. The study will involve assessments for side effects and tumor measurements.
Compensation
Not stated in the trial record.
Follow-up
Safety and tolerability will be measured for 6-12 months. Treatment discontinuations and dose modifications due to side effects will also be measured for 6-12 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT03526835

A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors

Recruiting
PHASE1Ages 18+InterventionalTreatment
Merus B.V.
~560 participants
Updated 2026-07-29 on ClinicalTrials.gov
What's tested:MCLA-158MCLA-158 + PembrolizumabMCLA-158 + FOLFIRIMCLA-158 + FOLFOX

At a glance

Recruiting sites
47 of 54 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Escalation: Number of patients with Dose Limiting Toxicities (DLTs) during Cycle 1
Measured over 4 weeks
+9 more outcomes measured

Conditions

Advanced/Metastatic Solid Tumors
Colorectal Cancer
Gastric Cancer
Gastroesophageal-junction Cancer
NSCLC
HNSCC
Head and Neck Squamous Cell Carcinoma
Esophageal Cancer

Explore related trials

Colorectal CarcinomaEsophageal CarcinomaGastric CarcinomaGastroesophageal Junction AdenocarcinomaHead and Neck Squamous Cell CarcinomaLung Non-Small Cell CarcinomaSolid NeoplasmMSI1 GeneProgrammed Cell Death 1 Ligand 1

NCT03526835

Where you'd take part

This study runs at 54 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, Italyno site contact published

    Recruiting

  • Cancer Care Northwest

    Spokane, Washingtonno site contact published

    Recruiting

  • Cayuga Medical Center

    Ithaca, New Yorkno site contact published

    Recruiting

  • Centre Antoine Lacassagne

    Nice, Franceno site contact published

    Recruiting

  • Centre Henri Becquerel

    Rouen, Franceno site contact published

    Recruiting

  • Centre Leon Berard

    Lyon, Franceno site contact published

    Recruiting

  • Chu Ucl Namur Site De Sainte-Elisabeth

    Namur, Belgiumno site contact published

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohiono site contact published

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Silke Thiele, MD · STUDY_DIRECTOR · Merus B.V.

Who to contact

Silke Thiele, MD
[email protected]
+31 85 016 2500
Email the study team

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Eligibility criteria

Inclusion

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:
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:
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.

Exclusion

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:

What this trial measures

  • Escalation: Number of patients with Dose Limiting Toxicities (DLTs) during Cycle 14 weeks

    Evaluation of the number and severity of participants with treatment related toxicities observed during the dose escalation.

  • Expansion (Single agent - randomized expansion in 2/3L Head and Neck cancer, and combination cohorts): Safety and tolerability: AEs and SAEs6-12 months

    Incidence, severity, and relationship of AEs and SAEs

  • Expansion (Single agent - randomized expansion in 2/3L Head and Neck cancer): Treatment discontinuations and dose modifications due to AEs6-12 months

    Treatment discontinuations due to AEs and dose modifications due to AEs

  • Expansion (single agent - randomized expansion in 2/3L Head and Neck cancer): Best overall response (BOR)36 months

    Evaluation of clinical benefit assessed by RECIST v1.1 determining Best overall response (BOR)

  • Expansion (Single agent - non-randomized, and combination cohorts): Objective response rate (ORR)36 months

    Evaluation of clinical benefit assessed by RECIST v1.1 determining objective response rate (ORR)

  • Expansion (single agent - randomized expansion in 2/3L Head and Neck cancer): exposure-safety relationship of petosemtamab administered at 1100 mg and 1500 mg: TEAEs8 weeks

    Incidence of TEAEs at Week 8

  • Expansion: (mCRC subcutaneous cohort): Bioavailability of subcutaneous vs intravenous administration6 weeks

    Bioavailability of subcutaneous vs intravenous administration

  • Expansion: (mCRC subcutaneous cohort): Area under the concentration versus time curve from time zero to time t [AUC0-t]6 weeks

    Area under the concentration versus time curve from time zero to time t \[AUC0-t\]

  • Expansion: (mCRC subcutaneous cohort): Maximum plasma concentration [Cmax]8 weeks

    Maximum plasma concentration as measured from all individual plasma concentrations

  • Expansion: (mCRC subcutaneous cohort): Minimum plasma drug concentration [Ctrough]6 weeks

    Minimum plasma concentration as measured from all individual plasma concentrations