A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors (eNRGy)
Study Identifier:
MCLA-128-CL01
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruitment Complete
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Study Summary
To study MCLA-128 in patients with solid tumors
To establish the MTD and Phase 2 recommended dose (RP2D) of MCLA-128 and to assess its safety, tolerability, PK, PD, and anti-tumor activity in selected patient (pt) groups.
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)
To assess the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers.
Part 2 will further characterize the safety and tolerability of the selected dose level of 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 12 weeks in duration). For this population, overall response rate (ORR) and duration of response (DOR) will be described.
exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC or other solid tumors.
This trial is designed in two parts: Part 1 (now complete) was dose escalation, and Part 2 is dose expansion, which further evaluates the safety and antitumor activity of Zeno. Part 2 initially evaluated the safety and efficacy of Zeno in non-NRG1+ cancer with aberrant HER2/HER3 signaling, such as breast cancer, ovarian cancer, gastric/gastroesophageal cancer and endometrial cancer.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
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:
- 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 ≥75x 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.
- Patients (pts) with advanced NRG1+ PDAC determined by NGS, previously treated with or not candidate for standard therapy, age ≥ 18 y, ECOG PS ≤ 2, and measurable (RECIST v1.1) or evaluable disease were enrolled.
- Patients (pts) with advanced NRG1+ NSCLC determined by NGS, previously treated with or not candidate for standard therapy, age ≥ 18 y, ECOG PS ≤ 2, and measurable (RECIST v1.1) or evaluable disease were enrolled.
- Inclusion Criteria
- • Locally advanced unresectable or metastatic solid tumor
- • NRG1+ cancer
- • Previously treated with or unable to receive standard therapy
- • ≥ 18 years of age
- • ECOG PS ≤ 2
- ≥ 1 dose of zenocutuzumab, opportunity for ≥ 24 weeks follow-up at the data cutoff date, documented NRG1 fusion by local tissue-based next-generation sequencing with predicted functionality, absence of other known driver mutations, completed a baseline tumor assessment within planned window, ≥ 1 postbaseline response assessment or early discontinuation due to disease progression, no exposure to prior anti-HER3 targeting antibodies
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.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Victor Moreno Garcia
Status
Recruitment Complete
Condition(s) Treated at Site
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Renal
Gastric
Solid Tumor
Soft Tissue Sarcoma
Endometrial
Esophageal
Neuroendocrine
Bile Duct