A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
NCT ID: NCT02912949
Last Updated: 2025-04-29
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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ACTIVE_NOT_RECRUITING
PHASE2
250 participants
INTERVENTIONAL
2015-01-31
2026-12-31
Brief Summary
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Detailed Description
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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 examine:
* Group F: Patients with NSCLC with documented NRG1 fusion
* Group G: Patients with pancreatic adenocarcinoma 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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
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.
zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
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.
zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
Interventions
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zenocutuzumab (MCLA-128)
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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. more than 14 days or more than 5 half-lives prior to study entry, whichever is shorter.
2. 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
* 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
* 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.
18 Years
ALL
No
Sponsors
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Partner Therapeutics, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Alison Schram, MD
Role: PRINCIPAL_INVESTIGATOR
Memorial Sloan Kettering Medical Center
Locations
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Mayo Clinic
Phoenix, Arizona, United States
The Oncology Institute of Hope and Innovation
Cerritos, California, United States
University of California Irvine
Irvine, California, United States
Stanford University
Palo Alto, California, United States
Sharp Memorial Hospital
San Diego, California, United States
Georgetown University
Washington D.C., District of Columbia, United States
Memorial Cancer Institute
Hollywood, Florida, United States
Cancer Specialists of North Florida
Jacksonville, Florida, United States
Mayo Clinic
Jacksonville, Florida, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
Northwest Oncology & Hematology
Rolling Meadows, Illinois, United States
Dana Farber Cancer Center
Boston, Massachusetts, United States
Karmanos Cancer Center
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Billings Clinic Cancer Center
Billings, Montana, United States
St. James Healthcare
Butte, Montana, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Averra Medical Group
Sioux Falls, South Dakota, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
Hematology-Oncology Specialist of Fredericksburg
Fredericksburg, Virginia, United States
Virginia Mason Hospital & Seattle Medical Center
Seattle, Washington, United States
Hematology Oncology Associates
Spokane, Washington, United States
Northwest Medical Specialties
Tacoma, Washington, United States
Salzburger Universitatsklinikum
Salzburg, , Austria
UZ Leuven
Leuven, , Belgium
Princess MargaretCancer Centre
Toronto, Ontario, Canada
Rigshospitalet
Copenhagen, , Denmark
Centre Leon Berard
Lyon, , France
Hospital Louis Pradel, FR
Lyon, , France
Institut Gustave Roussy
Paris, , France
Hopital Cochin
Paris, , France
Hopital Curie
Paris, , France
Asklepios Klinik Altona
Hamburg, , Germany
Asklepios Kliniken Hamburg GmbH
Hamburg, , Germany
Deutsches Krebsforschungszentrum
Heidelberg, , Germany
Shaare Zedek Medical Center
Jerusalem, , Israel
Sheba Medical Center
Tel Aviv, , Israel
Niguarda Cancer Centre
Milan, , Italy
Ospedale San Raffaele
Milan, , Italy
Istituti Fisioterapici Ospitalieri
Roma, , Italy
National Cancer Center Hospital
Chūōku, , Japan
St. Marianna University School of Medicine Hospital
Kawasaki, , Japan
Osaka International Cancer Institute
Osaka, , Japan
National Cancer Center East
Tokyo, , Japan
NKI
Amsterdam, , Netherlands
Amsterdam Medical Center
Amsterdam, , Netherlands
Radboud University Medical Center
Nijmegen, , Netherlands
University Hospital Oslo
Oslo, , Norway
National Cancer Centre of Singapore PTE LTD
Singapore, Singapore, Singapore
Samsung Medical Center
Seoul, , South Korea
Seoul National University College of Medicine
Seoul, , South Korea
Severance Hospital- Yonsei Cancer Center
Seoul, , South Korea
Vall D'Hebron Institute of Oncology (VHIO)
Barcelona, , Spain
START Hospital Fundación Jiménez Diaz
Madrid, , Spain
START Hospital Universitario Madrid Sanchinarro
Madrid, , Spain
Hospital 12 de Octubre
Madrid, , Spain
Clínica Universidad de Navarra
Pamplona, , Spain
Instituto Valenciano Oncologia
Valencia, , Spain
Karolinska Universitetssjukhuset
Solna, , Sweden
National Taiwan University Hospital 7
Taipei, , Taiwan
Sarah Cannon Research Institute
London, , United Kingdom
Countries
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References
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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.
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.
Related Links
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For more information about MCLA-128 and the MCLA-128-CL01 study
Other Identifiers
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2014-003277-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
MCLA-128-CL01
Identifier Type: -
Identifier Source: org_study_id
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