TriangleNCT02912949 · CITED IN SOURCE DOCUMENTS
A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-04-29
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)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- 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. 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: * 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
- intervention Names
- Drug: zenocutuzumab (MCLA-128)
- label
- Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion
- type
- EXPERIMENTAL
- description
- Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
- intervention Names
- Drug: zenocutuzumab (MCLA-128)
- label
- Part 2 NSCLC cancer harboring NRG1 fusion
- type
- EXPERIMENTAL
- description
- Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
- intervention Names
- Drug: zenocutuzumab (MCLA-128)
- label
- Part 2 Solid tumour (basket) harboring NRG1 fusion
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Part 2 NSCLC cancer harboring NRG1 fusion
- Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion
- Part 2 Solid tumour (basket) harboring NRG1 fusion
- description
- full length IgG1 bispecific antibody targeting HER2 and HER3
- name
- zenocutuzumab (MCLA-128)
- other Names
- bispecific
- MCLA-128
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 250
- type
- ESTIMATED
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
- measure
- Objective overall response rate (ORR) as per local investigator's assessment
- time Frame
- 36 months
- description
- To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally
- measure
- Duration of response per RECIST v1.1 as per local Investigator's assessment.
- time Frame
- 36 Months
- secondary Outcomes
- description
- Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1 as assessed centrally
- measure
- Overall response rate as per Blinded Independent Central Review (BICR)
- time Frame
- 36 months
- description
- 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 .
- measure
- Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and BICR
- time Frame
- 36 months
- description
- To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed centrally
- measure
- Duration of Response as per BICR
- time Frame
- 36 months
- description
- To assess time to onset of response in patients with NRG1 fusions as assessed locally
- measure
- Time to response per RECIST v1.1. as per local investigator assessment
- time Frame
- 36 months
- description
- To assess time to onset of response in patients with NRG1 fusions as assessed centrally
- measure
- Time to response per RECIST v1.1. as per BICR
- time Frame
- 36 months
- description
- Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)
- measure
- Characterize the safety and tolerability of zenocutuzumab (MCLA-128)
- time Frame
- 6-12 months
- description
- Assess the Cmax of zenocutuzumab (MCLA-128)
- measure
- Maximum plasma concentration [Cmax]
- time Frame
- 36 months
- description
- Assess the volume of distribution of zenocutuzumab (MCLA-128)
- measure
- Volume of distribution [V]
- time Frame
- 36 months
- description
- Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state
- measure
- Volume of distribution at steady state [Vss]
- time Frame
- 36 months
- description
- Assess the Area under the concentration versus time curve from time zero to time t \[AUC0-t\] of zenocutuzumab (MCLA-128)
- measure
- Area under the concentration versus time curve from time zero to time t [AUC0-t]
- time Frame
- 36 months
- description
- Assess the half-life of zenocutuzumab (MCLA-128)
- measure
- half-life [t1/2]
- time Frame
- 36 months
- description
- Assess the area under the concentration versus time curve \[AUC0-∞\] of zenocutuzumab (MCLA-128)
- measure
- area under the concentration versus time curve [AUC0-∞]
- time Frame
- 36 months
Full study description
- 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)
- 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 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.
Source references
- references
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- see Also Links
- label
- For more information about MCLA-128 and the MCLA-128-CL01 study
Source notices and limitations
Discovery and provenance
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- CAL STUDIES 14.1 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Non-Small Cell Lung Cancer The efficacy of BIZENGRI was evaluated in the eNRGy study (NCT02912949) a multicenter, open-label, multi-cohort clinical study. The study enrolled adult patients with advanced or metastatic NRG1 fusion-positive NSCLC who had disea
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- 1 PR NA 5.6 14.2 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Pancreatic Adenocarcinoma The efficacy of BIZENGRI was evaluated in the eNRGy study (NCT02912949), a multicenter, open-label, multi-cohort clinical study. The study enrolled 30 adult patients with advanced or metastatic NRG1 fusion-positive pancreatic aden
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- NA VTCN1 1 SD NA NA 14.3 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Cholangiocarcinoma The efficacy of BIZENGRI was evaluated in the eNRGy study (NCT02912949), a multicenter, open-label, multi-cohort clinical study. The study enrolled adult patients with advanced, unresectable or metastatic NRG1 fusion-positive chol
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Preserved source evidence · Not medical advice