RECRUITING

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

Conditions

Advanced/Metastatic Solid Tumors Colorectal Cancer Gastric Cancer Gastroesophageal-junction Cancer NSCLC HNSCC Head and Neck Squamous Cell Carcinoma Esophageal Cancer Bispecific antibody First-in-human MCLA-158 Antibodies Bispecific immunologic factors Cytokines EGFR LGR5

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase 1/2 open-label, multi-center, multi-national study with an initial dose escalation part to determine the recommended Phase II dose (RP2D) of MCLA-158 single agent in patients with mCRC. The dose escalation part has been completed and the RP2D will be further evaluated in an expansion part of the study. Cohorts of selected solid tumor indications for which there is evidence of EGFR dependency and potential sensitivity to EGFR inhibition will be evaluated including head and neck cancer and metastatic colorectal cancer (mCRC). The study will further assess the safety, tolerability, PK, PD, immunogenicity, and anti-tumor activity of MCLA-158 in monotherapy or in combination with other therapies.

Official Title

Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating MCLA-158 (Petosemtamab) as Single Agent or in Combination in Advanced Solid Tumors

Quick Facts

Study Start:2018-05-02

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03526835

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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: * 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) amplification, as detected in plasma by ctDNA NGS central testing performed during screening. * A microsatellite stable (MSS) tumor. * 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. * 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. * 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.	* 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: * Active hepatitis B infection ((hepatitis B surface antigen \[HBsAg\] positive) without receiving antiviral treatment. * 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.

Inclusion Criteria

Exclusion 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:
* 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) amplification, as detected in plasma by ctDNA NGS central testing performed during screening.
* A microsatellite stable (MSS) tumor.
* 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.
* 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.
* 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.

* 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:
* Active hepatitis B infection ((hepatitis B surface antigen \[HBsAg\] positive) without receiving antiviral treatment.
* 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.

Contacts and Locations

Study Contact

Gianluca Laus, MD

CONTACT

+31 85 016 2500

enquiries@merus.nl

Ernesto Wasserman, MD

CONTACT

+1 617 401 4499

USenquiries@merus.nl

Principal Investigator

Gianluca Laus, MD

STUDY_DIRECTOR

Merus N.V.

Study Locations (Sites)

UCSD

La Jolla, California, 92093

United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

Sharp Healthcare

San Diego, California, 92123

United States

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124

United States

Florida Cancer Specialists

Fort Myers, Florida, 33901

United States

Sarah Cannon Research Institute (Lake Nona)

Orlando, Florida, 32827

United States

Massachusetts General Hospital - Dana Farber

Boston, Massachusetts, 02114

United States

SSM Health Saint Louis University Hospital

Saint Louis, Missouri, 63110

United States

Washington University School of Medicine at St Louis

Saint Louis, Missouri, 63110

United States

Cayuga Medical Center

Ithaca, New York, 14850

United States

Hematology-Oncology Associates of Central New York

Syracuse, New York, 13057

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Taylor Cancer Research Center

Maumee, Ohio, 43537

United States

SSM OKC Hightower Clinical

Oklahoma City, Oklahoma, 73102

United States

The University Of Tennessee Health Science Center

Memphis, Tennessee, 38103

United States

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

United States

Texas Oncology

Dallas, Texas, 75246

United States

Oncology Consultants

Houston, Texas, 77030

United States

Texas Oncology

Tyler, Texas, 75702

United States

Utah Cancer Specialists

Salt Lake City, Utah, 84106

United States

University of Utah Health Huntsman Cancer Hospital

Salt Lake City, Utah, 84112

United States

Oncology & Hematology Associates of Southwest Virginia

Roanoke, Virginia, 24014

United States

Cancer Care Northwest

Spokane, Washington, 99202

United States

Collaborators and Investigators

Sponsor: Merus N.V.

Gianluca Laus, MD, STUDY_DIRECTOR, Merus N.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 Registration Dates

Study Start Date2018-05-02

Study Completion Date2027-11

Study Record Updates

Study Start Date2018-05-02

Study Completion Date2027-11

Terms related to this study

Keywords Provided by Researchers

Bispecific antibody
First-in-human
MCLA-158
Antibodies
Bispecific
immunologic factors
Cytokines
EGFR
LGR5

Additional Relevant MeSH Terms

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