Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer

May 22, 2026 updated by: Merus B.V.

A Phase 2 Study to Investigate the Safety and Efficacy of Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer in Combination With Pembrolizumab as First-Line Treatment

The study will test the efficacy and safety of petosemtamab in combination with Pembrolizumab in first line patients with squamous non-small cell lung cancer and non-squamous non-small cell lung cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Recruiting
        • Flinders Medical Centre
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Recruiting
        • Australia Site 1
  • France
      • Brest, France, 29609
        • Recruiting
        • CHU Brest Hopital la Cavale Blanche
      • Créteil, France, 94000
        • Recruiting
        • Centre Hospitalier Intercommunal de Creteil (CHIC)
      • Montpellier, France, 34298
        • Recruiting
        • ICM - Montpellier Cancer Institute
  • Italy
      • Florence, Italy, 50134
        • Recruiting
        • Universita degli Studi di Firenze - Azienda Ospedaliero-Universitaria Careggi
  • Netherlands
      • Leiden, Netherlands, 2333
        • Recruiting
        • Leiden University Medical Center
  • South Korea
      • Cheongju-si, South Korea, 28645
        • Recruiting
        • Chungbuk National University Hospital
      • Daegu, South Korea, 41404
        • Recruiting
        • Kyungpook National University Chilgok Hospital
      • Seoul, South Korea, 3722
        • Recruiting
        • Severance Hospital - Yonsei University Health System
  • Spain
      • Logroño, Spain, 26006
        • Recruiting
        • START - Rioja
  • United States
    • Florida
    • New York
      • Long Island City, New York, United States, 11101
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Recruiting
        • Tennessee Site 2
        • Contact:
      • Nashville, Tennessee, United States, 37209
        • Recruiting
        • Tennessee Site 1
        • Contact:
    • Virginia
      • Blacksburg, Virginia, United States, 24060
        • Recruiting
        • Virginia Site 2
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able to provide written informed consent and is willing and able to comply with all study procedures and contraception requirements
  • Age ≥ 18 years at the signing of ICF
  • At least 1 measurable lesion as defined by RECIST 1.1
  • ECOG performance status of 0 or 1
  • Life expectancy ≥ 12 weeks, in the opinion of the Investigator
  • Adequate hematologic function
  • Creatinine clearance ≥ 60 mL/min calculated according to the Cockroft and Gault formula
  • Adequate liver function
  • Serum albumin ≥ 3 g/dL
  • Serum magnesium and corrected calcium, Grade ≤ 1 alteration
  • Participants of childbearing potential must agree to use highly effective contraception methods for the duration of study participation
  • Histologically confirmed metastatic (Stage IV) sqNSCLC with PD-L1 TPS ≥ 50%
  • No prior systemic treatment for metastatic disease
  • Testing is required per local SOC and availability of testing to document absence of actionable genomic tumor aberrations
  • Histologically confirmed metastatic (Stage IV) non-squamous NSCLC with PD-L1 TPS ≥ 50%

Exclusion Criteria:

  • Has untreated CNS metastases and/or carcinomatous meningitis
  • Participation in an interventional clinical study with any investigational drug within 4 weeks prior to the first dose of study treatment OR participation in any clinical study with petosemtamab at any time prior to the first dose of study treatment, regardless of whether petosemtamab was received
  • Participants who received prior treatment with a PD-(L)1 inhibitor
  • Participants who have received prior systemic chemotherapy, targeted or biological antineoplastic therapy for metastatic NSCLC
  • Any systemic anticancer therapy within 4 weeks prior to the first dose of study treatment
  • Major surgery or radiotherapy within 3 weeks prior to the first dose of study treatment. Participants who received prior radiotherapy to ≥ 25% of bone marrow are not eligible, regardless of when it was received.
  • Persistent Grade > 1 clinically significant toxicities related to prior antineoplastic therapies using NCI-CTCAE v5.0
  • History of hypersensitivity reaction to any of the excipients of petosemtamab or pembrolizumab
  • Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association criteria or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia); or history of myocardial infarction within 6 months prior to the first dose of study treatment
  • History of prior malignancies within the last 5 years, with the exception of excised local cancer
  • Current dyspnea at rest of any origin or other diseases requiring continuous oxygen therapy, including participants with a history of ILD (eg, pneumonitis or pulmonary fibrosis) or evidence of ILD on baseline chest CT scan
  • Current serious illness or medical condition, including but not limited to uncontrolled active infection and clinically significant pulmonary, metabolic, or psychiatric disorders
  • Known infectious disease
  • Participants who are pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: First line squamous non-small cell lung cancer patients
Combination product: Petosemtamab + Pembrolizumab
Petosemtamab + Pembrolizumab
Experimental: First line non-squamous non-small cell lung cancer patients
Combination product: Petosemtamab + Pembrolizumab
Petosemtamab + Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate per investigator assessment
Time Frame: Up to 4.5 years
ORR was defined as the proportion of participants who had a complete response (CR) or partial response (PR) per RECIST v1.1.
Up to 4.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response per Investigator assessment
Time Frame: Up to 4.5 years
For participants with a confirmed CR or PR per RECIST v1.1, DOR was defined as the time from the date of first documented response of CR or PR per RECIST v1.1 to the date of first documented progression or death due to underlying cancer.
Up to 4.5 years
Disease control rate as per investigator assessment
Time Frame: Up to 4.5 years
DCR is defined as the proportion of participants with CR or PR or stable disease (SD) per RECIST 1.1.
Up to 4.5 years
Clinical Benefit Rate as per investigator assessment
Time Frame: Up to 4.5 years
CBR was defined as the proportion of participants with a CR or PR, or SD lasting ≥24 weeks per RECIST v1.1
Up to 4.5 years
Progression free survival as per investigator assessment
Time Frame: Up to 4.5 years
PFS was defined as the time from first dose to the first documented disease progression per RECIST v1.1 or death due to any cause.
Up to 4.5 years
Overall survival
Time Frame: Up to 4.5 years
OS was defined as the time from first dose to death due to any cause.
Up to 4.5 years
Number of participants who experienced on treatment adverse events
Time Frame: Up to 4.5 years
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Up to 4.5 years
Concentrations of petosemtamab predose and at end of infusion
Time Frame: Up to 6-12 months
Predose and end of infusion plasma concentrations as measured from all individual plasma concentrations.
Up to 6-12 months
Incidence and serum titers of anti-drug antibodies (ADAs) against petosemtamab
Time Frame: Up to 6-12 months
The frequency and proportion of participants developing anti-drug antibodies.
Up to 6-12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merus B.V.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2025

Primary Completion (Estimated)

May 31, 2028

Study Completion (Estimated)

February 27, 2031

Study Registration Dates

First Submitted

January 16, 2026

First Submitted That Met QC Criteria

January 16, 2026

First Posted (Actual)

January 21, 2026

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCLA-158-CL04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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