A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors
NCT ID: NCT03526835
Last Updated: 2025-01-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
523 participants
INTERVENTIONAL
2018-05-02
2027-11-30
Brief Summary
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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.
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Detailed Description
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This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose escalation to find the recommended Phase II dose (RP2D) of MCLA-158 studying patients with metastatic colorectal cancer (mCRC). Enrollment in the dose escalation part has been completed.
In the dose expansion (single-agent cohorts) part of the study, the activity, safety, and tolerability of MCLA-158 at 1500 mg every 2 weeks (Q2W) (preliminary RP2D) as a single agent will be evaluated in cohorts of selected solid tumor indications with dependency on EGFR signaling. The most recently enrolled cohorts were in patients with head and neck squamous cell carcinoma (HNSCC). Enrollment into the HNSCC cohort of single-agent MCLA-158 for the treatment of patients with second/third line (2L/3L) HNSCC is closed. In the dose expansion part of the study, safety was also characterized at two dose levels in this setting. Other closed cohort indications included gastric/gastroesophageal junction adenocarcinoma (GEA) with EGFR amplification and/or high EGFR expression, esophageal carcinoma, and pancreatic adenocarcinoma. Enrollment is currently being explored in mCRC (RAS/RAF wild type) patients in the 3L/4L/5L setting.
Additionally, in the dose expansion (combination cohorts) part of the study, the activity, safety, and tolerability of MCLA-158 at 1500 mg Q2W will be evaluated in combination with other therapies. Enrollment in the combination cohort of treatment of MCLA-158 with pembrolizumab for the treatment of patients with first line (1L) HNSCC is closed. Additionally, two combination cohorts of MCLA-158 with FOLFIRI or with FOLFOX chemotherapy (i.e., 5-fluorouracil \[5-FU\], leucovorin, and irinotecan (FOLFIRI) or oxaliplatin (FOLFOX)) will be explored in mCRC (RAS/RAF wild type) patients in the 1L/2L setting. Other expansion cohorts may be considered for monotherapy or combination treatment in the future.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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MCLA-158
In Part 1, the dose escalation phase, patients with metastatic CRC will receive escalating doses of MCLA-158 (every 2 weeks) until MTD or RP2D is reached. Each Cycle is 28 days. Single agent treatment.
In Part 2, the expansion phase, participants with metastatic CRC and certain other solid tumors will receive intravenous infusion of MCLA-158 at the recommended Phase II dose (RP2D) every 2 weeks, at Day 1 and Day 15. The duration of each treatment cycle is 28 days. In addition, in the expansion phase, one randomized cohort will evaluate 2 doses (1100 mg and 1500 mg) of MCLA-158 in head and neck squamous cell carcinoma patients.
MCLA-158
full-length IgG1 bispecific antibody targeting EGFR and LGR5
MCLA-158 + Pembrolizumab
MCLA-158 in combination with pembrolizumab will be explored first in head and neck squamous cell carcinoma patients eligible to receive pembrolizumab as first-line monotherapy.
MCLA-158 + Pembrolizumab
MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible to receive pembrolizumab as first-line monotherapy.
MCLA-158 + FOLFIRI combination chemotherapy
MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.
MCLA-158 + FOLFIRI
MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.
MCLA-158 + FOLFOX combination chemotherapy
MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.
MCLA-158 + FOLFOX
MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.
Interventions
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MCLA-158
full-length IgG1 bispecific antibody targeting EGFR and LGR5
MCLA-158 + Pembrolizumab
MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible to receive pembrolizumab as first-line monotherapy.
MCLA-158 + FOLFIRI
MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.
MCLA-158 + FOLFOX
MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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) amplification, as detected in plasma by ctDNA NGS central testing performed during screening.
* A microsatellite stable (MSS) tumor.
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.
* 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.
Exclusion Criteria
* 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.
18 Years
ALL
No
Sponsors
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Merus N.V.
INDUSTRY
Responsible Party
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Principal Investigators
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Gianluca Laus, MD
Role: STUDY_DIRECTOR
Merus N.V.
Locations
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UCSD
La Jolla, California, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Sharp Healthcare
San Diego, California, United States
Rocky Mountain Cancer Centers
Lone Tree, Colorado, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Sarah Cannon Research Institute (Lake Nona)
Orlando, Florida, United States
Massachusetts General Hospital - Dana Farber
Boston, Massachusetts, United States
SSM Health Saint Louis University Hospital
St Louis, Missouri, United States
Washington University School of Medicine at St Louis
St Louis, Missouri, United States
Cayuga Medical Center
Ithaca, New York, United States
Hematology-Oncology Associates of Central New York
Syracuse, New York, United States
Cleveland Clinic
Cleveland, Ohio, United States
Taylor Cancer Research Center
Maumee, Ohio, United States
SSM OKC Hightower Clinical
Oklahoma City, Oklahoma, United States
The University Of Tennessee Health Science Center
Memphis, Tennessee, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Texas Oncology
Dallas, Texas, United States
Oncology Consultants
Houston, Texas, United States
Texas Oncology
Tyler, Texas, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
University of Utah Health Huntsman Cancer Hospital
Salt Lake City, Utah, United States
Oncology & Hematology Associates of Southwest Virginia
Roanoke, Virginia, United States
Cancer Care Northwest
Spokane, Washington, United States
Cliniques universitaires Saint-Luc
Brussels, , Belgium
Institut Jules Bordet
Brussels, , Belgium
UZ Gent
Ghent, , Belgium
Chu Ucl Namur Site De Sainte-Elisabeth
Namur, , Belgium
Hopital Saint Andre, CHU Bordeaux
Bordeaux, , France
Centre Leon Berard
Lyon, , France
Hopital La Timone
Marseille, , France
Institut Régional du Cancer de Montpellier
Montpellier, , France
Centre Antoine Lacassagne
Nice, , France
Institut Curie
Paris, , France
Institut Gustave Roussy
Paris, , France
Centre Henri Becquerel
Rouen, , France
NKI - Antoni van Leeuwenhoek
Amsterdam, , Netherlands
UMC Radboud
Nijmegen, , Netherlands
UMC Utrecht
Utrecht, , Netherlands
Vall d'Hebron
Barcelona, , Spain
Hospital 12 de Octubre
Madrid, , Spain
Clinica Universidad de Navarra
Pamplona, , Spain
Hospital Universitario de Navarra
Pamplona, , Spain
Instituto Valenciano de Oncologia
Valencia, , Spain
Cambridge University Hospitals NHS Foundation Trust
Cambridge, , United Kingdom
Sarah Cannon Research Institute
London, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Petrea Monson
Role: primary
Sandy Tran
Role: primary
Danica Griffin
Role: primary
Jennifer Hege
Role: primary
Sufficient Bien
Role: primary
Ingrid Acker
Role: primary
Rowan Cutler
Role: primary
Olive Pressey
Role: primary
Danielle Rao
Role: primary
Kimberly Desimone
Role: primary
Stephanie Ambrose
Role: primary
Caitlin Merrick
Role: primary
Carlos Cortez
Role: primary
Devin Baxter
Role: primary
Krystal Swenson
Role: primary
Roxane Watterman
Role: primary
Sophie Coutinho-Coelho
Role: primary
Ellen De Bruycker, MD
Role: primary
Dominique Crasson
Role: primary
Delphine Padenon
Role: primary
Martin Porret
Role: primary
Leyla Ameur, MD
Role: primary
Justine Rochet
Role: primary
Morgane Sgorlon
Role: primary
Lucas Frezouls
Role: primary
Thinhinane Ould Taleb
Role: primary
Amelie Poullain
Role: primary
Lotte Heimans
Role: primary
Mirte Meijerinck
Role: primary
Sanne Bouwhuis
Role: primary
Antonio Molina
Role: primary
Mercedes Egana
Role: primary
Teresa Prieto
Role: primary
Valentina Achugo
Role: primary
Other Identifiers
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2017-004745-24
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2024-513627-16-01
Identifier Type: CTIS
Identifier Source: secondary_id
MCLA-158-CL01
Identifier Type: -
Identifier Source: org_study_id
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