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Clinical Trial 20848

Cancer Type: Gynecological Tumor
Study Type: Treatment
NCT#: NCT04590326

Phase: Phase I/II
Principal Investigator: Wenham, Robert

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

Phase I/II Study of REGN5668 (MUC16 x CD28, A Costimulatory Bispecific) Administered In Combination With Cemiplimab or REGN4018 (MUC16 x CD3)

Summary

The main purposes of this study are to: Learn about the safety and profile of any side effects from the study drugs and to determine the highest, safe dose that can be given to patients with ovarian cancer; Look for signs that the study drugs can treat ovarian cancer

Objective

Primary Objective: The primary objectives of the study are: In the Dose Escalation Phase: -To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or REGN4018, in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) these combinations. In the Dose Expansion Phase: -To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Secondary Objectives: The secondary objectives of the study are: In the Dose Escalation Phase: -To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1 In the Dose Expansion Phase: -To characterize the safety profile in each expansion cohort -To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) In both the Dose Escalation and Dose Expansion Phases: -To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separated by cohort and combination) as measured by ORR based on immune based therapy (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST -To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) -Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018 Exploratory Objectives: The exploratory objectives of the study are: -To evaluate biomarkers that may correlate with mechanism of action, increased understanding of disease/on-target activity, observed toxicity, and potential anti-tumor activity, or markers that may be predictors of efficacy and/or safety, which may include but are not limited to: -MUC16 and programmed cell death-ligand 1 (PD-L1) expression in tumors -Intratumoral and circulating immune cell populations -Plasma cytokine, chemokines and other circulating proteins -Intratumoral gene/transcript expression, tumor and circulating gene mutational burden -Where possible, to evaluate the relationship between exposure and efficacy, biomarker and safety endpoints -To assess overall survival (OS)

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

Cemiplimab (); REGN2810 (Cemiplimab); REGN4018 (); REGN5668 ()

Inclusion Criteria

Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has received at least 1 line of platinum-based systemic therapy as defined in the protocol

In dose escalation, patients will provide either newly obtained biopsy (newly obtained biopsies at screening are required unless medically inappropriate and discussed with medical monitor. If fresh biopsies are not appropriate, and after sponsor approval, archived tumor tissue in dose escalation is acceptable. In dose expansion, patients will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients who (in the opinion of the investigator) have accessible lesions that can be biopsied without significant risk to the patient are eligible.

Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation.

Has a serum CA-125 level > 2x ULN (in screening)

Has adequate organ and bone marrow function as defined in the protocol

Has a life expectancy of at least 3 months

Exclusion Criteria

Has participated in a study of an investigational agent (except biologics and/or immunotherapy) or an investigational device within 4 weeks of first dose of study drug

Has received treatment with an approved systemic therapy (except biologics and/or immunotherapy) within 3 weeks or has not yet recovered as defined in the protocol

Prior anti-cancer immunotherapy as defined in the protocol

Has received radiation therapy or major surgery within 14 days of first administration of study drug as defined in the protocol

Has had another malignancy within the last 5 years that is progressing, requires active treatment, or has a high likelihood of recurrence as defined in the protocol

Prior treatment with a MUC16-targeted therapy

Expansion cohorts only: More than 3 prior lines of cytotoxic chemotherapy for platinum-experienced and/or intolerant disease

Has any condition that requires ongoing/continuous corticosteroid therapy as defined in the protocol within 1 week prior to the first dose of study drug

Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol

Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol

Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study drug

Has history of clinically significant cardiovascular disease as defined in the protocol

Note: Other protocol-defined Inclusion/Exclusion criteria apply

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