Ph I/II Study of MCLA-128, IgG1 Bispecific Antibody Targeting HER2 & HER3, in Pts w/ Solid Tumors
Study Description
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.
Eligibility
At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 10) in Group H;
Performance status of ECOG 0 or 1;
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:
>14 days or >5 half-lives prior to study entry, whichever is shorter.
>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;
Platelets ≥100 x 109/L;
Hemoglobin ≥8 g/dL or ≥2.2 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
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 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 congestive heart failure or Left Ventricular Ejection Fraction<50% or history of significant cardiac disease, unstable angina, myocardial infarction 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.
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