A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients with Solid Tumors

Cancer Categories

Lung

Karmanos Trial ID

2019-121

NCT ID

NCT02912949

Age Group

Adult

Scope

National

Phase

Phase I/II

Principal Investigator

Mohammed Najeeb
Al Hallak, M.D., MS
Oncology - Medical View Profile

Objective:

Part 1 Primary Objective:

Determination of the MTD and/or MRD of MCLA-128.

Secondary Objectives:

To characterize the safety and tolerability of MCLA-128.
PK profile of MCLA-128.
Immunogenicity of MCLA-128.
Evaluation of anti-tumor response and clinical benefit rate (CBR).

Part 2 Primary Safety Objective:

To characterize the safety and tolerability of MCLA-128.

Primary Efficacy Objectives:

To explore the relationships between the anti-tumor activity of MCLA-128 and disease-related biomarkers
To assess magnitude of anti-tumor activity of MCLA-128 in patients with NRG1 fusion (Cohorts F, G, H)

Key Secondary Objective:

To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions (Cohorts F, G, H)

Secondary Objectives:

PK profile of MCLA-128.
Immunogenicity of MCLA-128.
Evaluation of PFS and overall survival, duration of response

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Eligibility

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:

>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 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 >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 <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's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices