A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)

January 12, 2024 updated by: Merus N.V.

A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors (eNRGy)

This is a Phase I/II, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, PK, PD, immunogenicity and anti-tumor activity of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Design :

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed.

Part 2 new patient populations examined:

  • Group F: Patients with NSCLC with documented NRG1 fusion
  • Group G: Patients with pancreatic adenocarcinoma with documented NRG1 fusion
  • Group H: Patients with any other solid tumor with documented NRG1 fusion

For these new patient populations, Part 2 will further characterize the safety and tolerability of the selected dose level of zenocutuzumab (MCLA-128), as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 24 weeks in duration). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described.

The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (treatment cycles of 28 days); and Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 2 years). Participants' safety will be monitored throughout the study.

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

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

  • Name: Merus Inquiries
  • Phone Number: 1-833-NRG-1234

Study Locations

  • Austria
      • Salzburg, Austria
        • Recruiting
        • Salzburger Universitatsklinikum
        • Contact:
          • Richard Greil, MD
  • Belgium
      • Leuven, Belgium
        • Recruiting
        • UZ Leuven
        • Contact:
          • Jeroen Dekervel, MD
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G2M9
        • Recruiting
        • Princess MargaretCancer Centre
        • Contact:
          • Erika Tsang, MD
  • Denmark
      • Copenhagen, Denmark
        • Recruiting
        • Rigshospitalet
        • Principal Investigator:
          • Kristoffer Rohrberg
  • France
      • Lyon, France
        • Recruiting
        • Centre Léon Bérard
        • Principal Investigator:
          • Philippe Cassier, MD
      • Lyon, France
        • Recruiting
        • Hospital Louis Pradel, FR
        • Contact:
          • Michael Duruisseaux, MD
        • Principal Investigator:
          • Michael Duruisseaux, MD
      • Paris, France
        • Recruiting
        • Hôpital COCHIN
        • Contact:
          • Marie Wislez, MD
      • Paris, France, 94805
        • Recruiting
        • Institut Gustave Roussy
        • Contact:
          • Elodie Zedouard
        • Principal Investigator:
          • Antoine Hollebecque, MD
      • Paris, France
        • Recruiting
        • Hopital Curie
        • Contact:
          • Cindy NEUZILLET, MD
  • Germany
      • Hamburg, Germany
        • Recruiting
        • Asklepios Klinik Altona
        • Contact:
          • Dirk Arnold, MD
      • Hamburg, Germany
        • Recruiting
        • Asklepios Kliniken Hamburg GmbH
        • Contact:
          • Claas Wesseler, MD
      • Heidelberg, Germany
        • Recruiting
        • Deutsches Krebsforschungszentrum
        • Contact:
          • Christoph Springfeld, MD
  • Israel
      • Jerusalem, Israel
        • Recruiting
        • Shaare Zedek Medical Center
        • Contact:
          • Nir Peled, MD
      • Tel Aviv, Israel
        • Recruiting
        • Sheba Medical Center
        • Contact:
          • Talia Golan, MD
  • Italy
      • Milan, Italy, 20162
        • Recruiting
        • Niguarda Cancer Centre
        • Contact:
          • Salvatore Siena, Prof
        • Contact:
          • Giovanna Marrapese
        • Principal Investigator:
          • Salvatore Siena, Prof
      • Milano, Italy
        • Recruiting
        • Ospedale San Raffaele
        • Contact:
          • Michele Reni, MD
      • Roma, Italy
        • Recruiting
        • Istituti Fisioterapici Ospitalieri
        • Contact:
          • Federico Cappuzzo, MD
  • Japan
      • Chuo-Ku, Japan
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
          • Chigusa Morizane, MD
      • Kawasaki, Japan
        • Recruiting
        • St. Marianna University School of Medicine Hospital
        • Contact:
          • Yu Sunakawa, MD
      • Osaka, Japan
        • Recruiting
        • Osaka International Cancer Institute
        • Contact:
          • Kazumi Nishino, MD
      • Tokyo, Japan
        • Recruiting
        • National Cancer Center East
        • Contact:
          • Koichi Goto, MD
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Joon Oh Park, MD
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University College of Medicine
        • Contact:
          • Kim Dong-Wan, MD
        • Principal Investigator:
          • Kim Dong-Wan, MD
      • Seoul, Korea, Republic of
        • Recruiting
        • Severance Hospital- Yonsei Cancer Center
        • Contact:
          • Sun Young Rha, MD
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • NKI
        • Principal Investigator:
          • Frans Opdam, MD
      • Amsterdam, Netherlands
        • Recruiting
        • Amsterdam Medical Center
        • Contact:
          • Hanneke Wilmink, MD
      • Nijmegen, Netherlands
        • Recruiting
        • Radboud University Medical Center
        • Contact:
          • Elske Gootjes, MD
      • Utrecht, Netherlands, 3584CX
  • Norway
      • Oslo, Norway, 0379
        • Recruiting
        • University Hospital Oslo
        • Principal Investigator:
          • Tormod Guren, Dr.
  • Singapore
      • Singapore, Singapore
        • Recruiting
        • National Cancer Centre of Singapore PTE LTD
        • Contact:
          • Daniel Shao Weng, MD
        • Principal Investigator:
          • Justina Lam, MD
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d'Hebron Institute of Oncology (VHIO)
        • Principal Investigator:
          • Teresa Macarulla, MD
        • Contact:
      • Madrid, Spain, 28040
        • Recruiting
        • START Hospital Fundación Jiménez Diaz
        • Contact:
          • Adriana Armellini
        • Principal Investigator:
          • Victor Moreno, Dr.
      • Madrid, Spain, 28050
        • Recruiting
        • START Hospital Universitario Madrid Sanchinarro
        • Contact:
          • Esther Ordoñez
        • Principal Investigator:
          • Irene Moreno, Dr.
      • Madrid, Spain
        • Recruiting
        • Hospital 12 de Octubre
        • Contact:
          • Luis Paz-Ares, MD
        • Principal Investigator:
          • Luis Paz-Ares, MD
      • Pamplona, Spain
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Miguel Fernandez de Sanmamed Gutierrez, MD
      • Valencia, Spain
        • Recruiting
        • Instituto Valenciano Oncologia
        • Contact:
          • Desamparados Roda, MD
  • Sweden
      • Solna, Sweden
        • Recruiting
        • Karolinska Universitetssjukhuset
        • Contact:
          • Jeffrey Yachnin, MD
  • Taiwan
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital 7
        • Contact:
          • James Yang Chih-Hsin, MD
        • Principal Investigator:
          • James Yang Chih-Hsin
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
          • Elisa Fontana, MD
  • United States
    • Arizona
      • Phoenix, Arizona, United States
        • Completed
        • Mayo Clinic
    • California
      • Cerritos, California, United States
        • Recruiting
        • The Oncology Institute of Hope and Innovation
        • Principal Investigator:
          • Paul La Porte
      • Irvine, California, United States
        • Recruiting
        • University of California Irvine
        • Contact:
          • MD
        • Principal Investigator:
          • Misako Nagasaka, MD
      • Palo Alto, California, United States
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Christopher Chen, MD
      • San Diego, California, United States
        • Recruiting
        • Sharp Memorial Hospital
        • Principal Investigator:
          • Charles Redfern
    • District of Columbia
      • Washington, District of Columbia, United States
        • Recruiting
        • Georgetown University
        • Contact:
          • Stephen Liu, MD
          • Phone Number: 202-687-9861
        • Principal Investigator:
          • Stephen Liu, MD
    • Florida
      • Hollywood, Florida, United States
        • Recruiting
        • Memorial Cancer Institute
        • Principal Investigator:
          • Luis Raez, MD
      • Jacksonville, Florida, United States
        • Recruiting
        • Cancer Specialists of North Florida
        • Contact:
          • Study Coordinator
          • Phone Number: 904-538-4488
      • Jacksonville, Florida, United States
        • Completed
        • Mayo Clinic
    • Georgia
      • Atlanta, Georgia, United States
        • Recruiting
        • Emory Winship Cancer Institute
        • Contact:
          • Study Coordinator
          • Phone Number: 404-778-0032
    • Illinois
      • Rolling Meadows, Illinois, United States
        • Recruiting
        • Northwest Oncology & Hematology
        • Principal Investigator:
          • Bruce Bank
    • Massachusetts
      • Boston, Massachusetts, United States
        • Recruiting
        • Dana Farber Cancer Center
        • Contact:
          • James Cleary, MD
          • Phone Number: 617-632-6623
        • Principal Investigator:
          • James Cleary, MD
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Center
        • Contact:
          • Jaclyn Ventimiglia
          • Phone Number: 313-576-9813
        • Principal Investigator:
          • Mohammed Najeeb Al Hallak
    • Minnesota
      • Rochester, Minnesota, United States
        • Completed
        • Mayo Clinic
    • Montana
      • Billings, Montana, United States
        • Recruiting
        • Billings Clinic Cancer Center
        • Contact:
          • Study Coordinator
          • Phone Number: 406-238-2500
      • Butte, Montana, United States
        • Completed
        • St. James Healthcare
    • New York
      • New York, New York, United States
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Alison Schram, MD
          • Phone Number: 646-888-4226
        • Principal Investigator:
          • Alison Schram
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Study Coordinator
          • Phone Number: 215-220-9711
    • South Dakota
      • Sioux Falls, South Dakota, United States
        • Completed
        • Averra Medical Group
    • Texas
      • Houston, Texas, United States
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
          • Jordi Rodon, MD
          • Phone Number: 713-563-1930
        • Principal Investigator:
          • Jordi Rodon
    • Utah
      • Salt Lake City, Utah, United States
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
          • Study Coordinator
          • Phone Number: 801-587-7000
      • Salt Lake City, Utah, United States
        • Recruiting
        • Utah Cancer Specialists
        • Contact:
          • Study Coordinator
          • Phone Number: 801-270-2243
    • Virginia
      • Fredericksburg, Virginia, United States
        • Recruiting
        • Hematology-Oncology Specialist of Fredericksburg
        • Contact:
          • Study Coordinator
          • Phone Number: 540-371-0079
    • Washington
      • Seattle, Washington, United States
        • Recruiting
        • Virginia Mason Hospital & Seattle Medical Center
        • Contact:
          • Study Coordinator
          • Phone Number: 206-223-6193
      • Spokane, Washington, United States
        • Recruiting
        • Hematology Oncology Associates
        • Contact:
          • Study Staff
          • Phone Number: 509-462-2273
      • Tacoma, Washington, United States
        • Recruiting
        • Northwest Medical Specialties
        • Contact:

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 15) in Group H;
  • Performance status of ECOG 0 - 2;
  • Estimated life expectancy of at least 12 weeks;
  • Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1;

  • Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:

    1. >14 days or >5 half-lives prior to study entry, whichever is shorter.
    2. >14 days for radiotherapy.
  • Recovery from major surgery or other complication to ≤ Grade 2 or baseline ;
  • Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support for at least 7 days prior to screening;
  • Platelets ≥75 x 109/L without transfusion support for at least 7 days prior to screening;
  • Hemoglobin ≥8 g/dL or ≥5 mmol/L;
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN; in cases of metastatic liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed; in cases of antecedents of Gilbert's syndrome when total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN will be allowed;
  • Estimated glomerular filtration rate (GFR) of >30 mL/min
  • Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
  • Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available;
  • Locally-advanced unresectable or metastatic solid tumor malignancy with documented NRG1 gene fusion, identified through molecular assays such as next generation sequencing-based assays [DNA or RNA], as routinely performed at CLIA or other similarly-certified laboratories.

Exclusion Criteria:

  • Pregnant or lactating;
  • Presence of an active uncontrolled infection or an unexplained fever;
  • Known hypersensitivity to any of the components of MCLA-128;
  • Known HIV, active Hepatitis B without receiving antiviral treatment, or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
  • Known symptomatic or unstable brain metastases;
  • Patients with leptomeningeal metastases;
  • Presence of LVEF <50% on the screening echocardiogram; or history or presence of any significant cardiovascular disease, including unstable angina or myocardial infarction within 12 months prior to screening, congestive heart failure (NYHA Class III or IV), or ventricular arrhythmia requiring medication;
  • Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
  • Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

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: Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Names:
  • bispecific
  • MCLA-128
Experimental: Part 2 NSCLC cancer harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Names:
  • bispecific
  • MCLA-128
Experimental: Part 2 Solid tumour (basket) harboring NRG1 fusion
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
Drug: zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Names:
  • bispecific
  • MCLA-128

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective overall response rate (ORR) as per local investigator's assessment
Time Frame: 36 months
Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
36 months
Duration of response per RECIST v1.1 as per local Investigator's assessment.
Time Frame: 36 Months
To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally
36 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration [Cmax]
Time Frame: 36 months
Assess the Cmax of zenocutuzumab (MCLA-128)
36 months
Volume of distribution [V]
Time Frame: 36 months
Assess the volume of distribution of zenocutuzumab (MCLA-128)
36 months
Volume of distribution at steady state [Vss]
Time Frame: 36 months
Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state
36 months
half-life [t1/2]
Time Frame: 36 months
Assess the half-life of zenocutuzumab (MCLA-128)
36 months
Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame: 36 months
Assess the Area under the concentration versus time curve from time zero to time t [AUC0-t] of zenocutuzumab (MCLA-128)
36 months
area under the concentration versus time curve [AUC0-∞]
Time Frame: 36 months
Assess the area under the concentration versus time curve [AUC0-∞] of zenocutuzumab (MCLA-128)
36 months
time to reach maximum concentration [tmax]
Time Frame: 36 months
Assess the time to reach maximum concentration [tmax] of zenocutuzumab (MCLA-128)
36 months
Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
Time Frame: 36 months
Assess the Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
36 months
serum titers of anti-drug antibodies
Time Frame: 36 months
Assess serum titers of anti-drug antibodies
36 months
Overall response rate as per central review
Time Frame: 36 months
Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1 as assessed centrally
36 months
Duration of Response as per central review
Time Frame: 36 months
To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed centrally
36 months
Time to response per RECIST v1.1. as per local Investigator's assessment.
Time Frame: 36 months
To assess time to onset of response in patients with NRG1 fusions as assessed locally
36 months
Time to response per RECIST v1.1. as per central review
Time Frame: 36 months
To assess time to onset of response in patients with NRG1 fusions as assessed centrally
36 months
Characterize the safety and tolerability of zenocutuzumab (MCLA-128)
Time Frame: 6-12 months
Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)
6-12 months
Evaluation of progression free survival (PFS)
Time Frame: 36 months
36 months
Evaluation of overall survival (OS)
Time Frame: 12 months
12 months
Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and centrally
Time Frame: 36 months
CBR assessed as the proportion of patients in whom a complete response (CR) or partial response (PR) or stable disease (SD) is observed (where SD duration is a minimum of 24 weeks) by RECIST v1.1 .
36 months

Collaborators and Investigators

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

Sponsor

Merus N.V.

Investigators

  • Principal Investigator: Alison Schram, MD, Memorial Sloan Kettering Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

January 1, 2015

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

August 16, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimated)

September 23, 2016

Study Record Updates

Last Update Posted (Estimated)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCLA-128-CL01
  • 2014-003277-42 (EudraCT Number)

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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