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

NCT02912949 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCLA-128-CL012014-003277-42
• Study Type: interventional
• Target: 250
• Locations: 18 countries
• Sites: 64

Brief Summary

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)

Conditions

Solid Tumours Harboring NRG1 Fusion; NSCLC Harboring NRG1 Fusion; Pancreatic Cancer Harboring NRG1 Fusion; NRG1 Fusion

Keywords

Bispecific Antibody IgG1, HER2, HER3; MCLA-128; Antibodies, Bispecific; Immunologic Factors; NRG1 fusion; Solid tumor; Pancreatic cancer; PDAC; Non-small cell lung cancer; NSCLC; zenocutuzumab

Outcome Measures

Primary Outcomes (2)

• Objective overall response rate (ORR) as per local investigator's assessment

  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.

  To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally

  36 Months

Secondary Outcomes (17)

• Overall response rate as per Blinded Independent Central Review (BICR)

  36 months

• Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and BICR

  36 months

• Duration of Response as per BICR

  36 months

• Time to response per RECIST v1.1. as per local investigator assessment

  36 months

• Time to response per RECIST v1.1. as per BICR

  36 months

Study Arms (3)

Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion

EXPERIMENTAL

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)

Part 2 NSCLC cancer harboring NRG1 fusion

EXPERIMENTAL

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)

Part 2 Solid tumour (basket) harboring NRG1 fusion

EXPERIMENTAL

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)

Interventions

zenocutuzumab (MCLA-128) DRUG

full length IgG1 bispecific antibody targeting HER2 and HER3

Also known as: bispecific, MCLA-128

Part 2 NSCLC cancer harboring NRG1 fusion; Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion; Part 2 Solid tumour (basket) harboring NRG1 fusion

Eligibility Criteria

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

You may qualify if:

• 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:
• more than 14 days or more than 5 half-lives prior to study entry, whichever is shorter.
• more than 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 more than 30 mL/min
• Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
• Not pregnant or nursing

You may not qualify if:

• 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 below 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 ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Sponsors & Collaborators

• Partner Therapeutics, Inc.: lead

Study Sites (64)

Mayo Clinic

Phoenix, Arizona, United States

Location

The Oncology Institute of Hope and Innovation

Cerritos, California, United States

Location

University of California Irvine

Irvine, California, United States

Location

Stanford University

Palo Alto, California, United States

Location

Sharp Memorial Hospital

San Diego, California, United States

Location

Georgetown University

Washington D.C., District of Columbia, United States

Location

Memorial Cancer Institute

Hollywood, Florida, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Location

Mayo Clinic

Jacksonville, Florida, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Location

Northwest Oncology & Hematology

Rolling Meadows, Illinois, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Billings Clinic Cancer Center

Billings, Montana, United States

Location

St. James Healthcare

Butte, Montana, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

Averra Medical Group

Sioux Falls, South Dakota, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, United States

Location

Hematology-Oncology Specialist of Fredericksburg

Fredericksburg, Virginia, United States

Location

Virginia Mason Hospital & Seattle Medical Center

Seattle, Washington, United States

Location

Hematology Oncology Associates

Spokane, Washington, United States

Location

Northwest Medical Specialties

Tacoma, Washington, United States

Location

Salzburger Universitatsklinikum

Salzburg, Austria

Location

UZ Leuven

Leuven, Belgium

Location

Princess MargaretCancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

Rigshospitalet

Copenhagen, Denmark

Location

Centre Leon Berard

Lyon, France

Location

Hospital Louis Pradel, FR

Lyon, France

Location

Institut Gustave Roussy

Paris, 94805, France

Location

Hopital Cochin

Paris, France

Location

Hopital Curie

Paris, France

Location

Asklepios Klinik Altona

Hamburg, Germany

Location

Asklepios Kliniken Hamburg GmbH

Hamburg, Germany

Location

Deutsches Krebsforschungszentrum

Heidelberg, Germany

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Sheba Medical Center

Tel Aviv, Israel

Location

Niguarda Cancer Centre

Milan, 20162, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Istituti Fisioterapici Ospitalieri

Roma, Italy

Location

National Cancer Center Hospital

Chūōku, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

National Cancer Center East

Tokyo, Japan

Location

NKI

Amsterdam, 1066 CX, Netherlands

Location

Amsterdam Medical Center

Amsterdam, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

University Hospital Oslo

Oslo, 0379, Norway

Location

National Cancer Centre of Singapore PTE LTD

Singapore, Singapore, Singapore

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University College of Medicine

Seoul, South Korea

Location

Severance Hospital- Yonsei Cancer Center

Seoul, South Korea

Location

Vall D'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

START Hospital Fundación Jiménez Diaz

Madrid, 28040, Spain

Location

START Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

Instituto Valenciano Oncologia

Valencia, Spain

Location

Karolinska Universitetssjukhuset

Solna, Sweden

Location

National Taiwan University Hospital 7

Taipei, Taiwan

Location

Sarah Cannon Research Institute

London, United Kingdom

Location

Related Publications (2)

• Schram AM, Goto K, Kim DW, Macarulla T, Hollebecque A, O'Reilly EM, Ou SI, Rodon J, Rha SY, Nishino K, Duruisseaux M, Park JO, Neuzillet C, Liu SV, Weinberg BA, Cleary JM, Calvo E, Umemoto K, Nagasaka M, Springfeld C, Bekaii-Saab T, O'Kane GM, Opdam F, Reiss KA, Joe AK, Wasserman E, Stalbovskaya V, Ford J, Adeyemi S, Jain L, Jauhari S, Drilon A; eNRGy Investigators. Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer. N Engl J Med. 2025 Feb 6;392(6):566-576. doi: 10.1056/NEJMoa2405008.

  PMID: 39908431 DERIVED

• Kim DW, Schram AM, Hollebecque A, Nishino K, Macarulla T, Rha SY, Duruisseaux M, Liu SV, Al Hallak MN, Umemoto K, Wesseler C, Cleary JM, Springfeld C, Neuzillet C, Joe A, Jauhari S, Ford J, Goto K. The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions. Future Oncol. 2024;20(16):1057-1067. doi: 10.2217/fon-2023-0824. Epub 2024 Feb 13.

  PMID: 38348690 DERIVED

Related Links

• For more information about MCLA-128 and the MCLA-128-CL01 study

MeSH Terms

Conditions

Lethal Congenital Contracture Syndrome 2; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

zenocutuzumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alison Schram, MD

  Memorial Sloan Kettering Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: September 23, 2016
• Study Start: January 1, 2015
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1); US (26); BE (1); DE (3); IL (2); NO (1); SG (1); ES (6); FR (5); GB (1); KR (3); AU (1); CA (1); IT (3); SE (1); DK (1); NL (3); JP (4)