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

NCT03526835 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MCLA-158-CL012017-004745-242024-513627-16-01
• Study Type: interventional
• Target: 523
• Locations: 6 countries
• Sites: 45

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Escalation: Number of patients with Dose Limiting Toxicities (DLTs) during Cycle 1

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

  4 weeks

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

  Incidence, severity, and relationship of AEs and SAEs

  6-12 months

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

  Treatment discontinuations due to AEs and dose modifications due to AEs

  6-12 months

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

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

  36 months

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

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

  36 months

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

  Incidence of TEAEs at Week 8

  8 weeks

Secondary Outcomes (24)

• Escalation & Expansion: Duration of response (DOR)

  36 months

• Expansion: Progression Free Survival (PFS)

  36 months

• Expansion (mCRC combination cohorts): Progression Free Survival (PFS) rate at 4 months

  4 months

• Expansion (Single agent - non-randomized cohorts): Overall survival (OS)

  36 months

• Escalation & Expansion (single agent - non-randomized cohorts): Safety and tolerability: AEs and SAEs

  up to 30 days post-last dose

Study Arms (4)

MCLA-158

EXPERIMENTAL

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.

Drug: MCLA-158

MCLA-158 + Pembrolizumab

EXPERIMENTAL

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.

Combination Product: MCLA-158 + Pembrolizumab

MCLA-158 + FOLFIRI combination chemotherapy

EXPERIMENTAL

MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.

Combination Product: MCLA-158 + FOLFIRI

MCLA-158 + FOLFOX combination chemotherapy

EXPERIMENTAL

MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.

Combination Product: MCLA-158 + FOLFOX

Interventions

MCLA-158 DRUG

full-length IgG1 bispecific antibody targeting EGFR and LGR5

Also known as: petosemtamab

MCLA-158

MCLA-158 + Pembrolizumab COMBINATION_PRODUCT

MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible to receive pembrolizumab as first-line monotherapy.

Also known as: petosemtamab

MCLA-158 + Pembrolizumab

MCLA-158 + FOLFIRI COMBINATION_PRODUCT

MCLA-158 in combination with FOLFIRI will be explored in mCRC patients with up to 1 line of prior regimen.

Also known as: petosemtamab

MCLA-158 + FOLFIRI combination chemotherapy

MCLA-158 + FOLFOX COMBINATION_PRODUCT

MCLA-158 in combination with FOLFOX will be explored in mCRC patients with up to 1 line of prior regimen.

Also known as: petosemtamab

MCLA-158 + FOLFOX combination chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• L+ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (45)

UCSD

La Jolla, California, 92093, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Sharp Healthcare

San Diego, California, 92123, United States

RECRUITING

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States

RECRUITING

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

RECRUITING

Sarah Cannon Research Institute (Lake Nona)

Orlando, Florida, 32827, United States

RECRUITING

Massachusetts General Hospital - Dana Farber

Boston, Massachusetts, 02114, United States

RECRUITING

SSM Health Saint Louis University Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Washington University School of Medicine at St Louis

St Louis, Missouri, 63110, United States

RECRUITING

Cayuga Medical Center

Ithaca, New York, 14850, United States

RECRUITING

Hematology-Oncology Associates of Central New York

Syracuse, New York, 13057, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

SSM OKC Hightower Clinical

Oklahoma City, Oklahoma, 73102, United States

RECRUITING

The University Of Tennessee Health Science Center

Memphis, Tennessee, 38103, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

COMPLETED

Texas Oncology

Dallas, Texas, 75246, United States

RECRUITING

Oncology Consultants

Houston, Texas, 77030, United States

RECRUITING

Texas Oncology

Tyler, Texas, 75702, United States

RECRUITING

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

RECRUITING

University of Utah Health Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

RECRUITING

Oncology & Hematology Associates of Southwest Virginia

Roanoke, Virginia, 24014, United States

RECRUITING

Cancer Care Northwest

Spokane, Washington, 99202, United States

RECRUITING

Cliniques universitaires Saint-Luc

Brussels, Belgium

RECRUITING

Institut Jules Bordet

Brussels, Belgium

RECRUITING

UZ Gent

Ghent, Belgium

RECRUITING

Chu Ucl Namur Site De Sainte-Elisabeth

Namur, Belgium

RECRUITING

Hopital Saint Andre, CHU Bordeaux

Bordeaux, France

RECRUITING

Centre Leon Berard

Lyon, France

RECRUITING

Hopital La Timone

Marseille, France

RECRUITING

Institut Régional du Cancer de Montpellier

Montpellier, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Institut Curie

Paris, France

RECRUITING

Institut Gustave Roussy

Paris, France

RECRUITING

Centre Henri Becquerel

Rouen, France

RECRUITING

NKI - Antoni van Leeuwenhoek

Amsterdam, Netherlands

RECRUITING

UMC Radboud

Nijmegen, Netherlands

RECRUITING

UMC Utrecht

Utrecht, Netherlands

RECRUITING

Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Spain

RECRUITING

Hospital Universitario de Navarra

Pamplona, Spain

RECRUITING

Instituto Valenciano de Oncologia

Valencia, Spain

RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

COMPLETED

Sarah Cannon Research Institute

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Neoplasms

Interventions

pembrolizumab; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Esophageal Diseases

Study Officials

• Gianluca Laus, MD

  Merus B.V.

  STUDY DIRECTOR

Central Study Contacts

Gianluca Laus, MD

CONTACT

+31 85 016 2500; enquiries@merus.nl

Ernesto Wasserman, MD

CONTACT

+1 617 401 4499; USenquiries@merus.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: May 16, 2018
• Study Start: May 2, 2018
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2027
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); FR (8); NL (3); US (23); GB (2); BE (4)