Last updated on March 2020

A Phase 1/2 Study of CYT-0851 an Oral RAD51 Inhibitor in B-Cell Malignancies and Advanced Solid Tumors


Brief description of study

This clinical trial is an interventional, active-treatment, open-label, multi-center, Phase 1/2 study. The study objectives are to assess the safety, tolerability and pharmacokinetics (PK) of the oral RAD51 inhibitor CYT-0851 in patients with relapsed/refractory B-cell malignancies and advanced solid tumors and to identify a recommended Phase 2 dose for evaluation in these patients.

Detailed Study Description

Overexpression of activation-induced cytidine deaminase (AID) or other cytidine deaminases causes high rates of deoxyribonucleic acid (DNA) damage (mutations, double strand DNA breaks, and chromosome rearrangements) in a high number of patients with B-cell malignancies, such as NHL, MM, and CLL, and in a subset of patients with solid tumors, such as non-small cell lung cancer (NSCLC), sarcoma, breast cancer, ovarian cancer, and squamous cell carcinoma of the head and neck. Cancer cells that overexpress AID and other cytidine deaminases rely on RAD51, a protein involved in homologous recombination, to repair the DNA damage caused by cytidine deaminases. Inhibition of RAD51 with CYT-0851 in preclinical models induces cell death, tumor growth delay or tumor regression.

The Phase 1 part of the study will follow an accelerated titration design, which includes enrollment of single patient cohorts until certain criteria are met, followed by a standard 3+3 design. This design will allow for identification of a recommended phase 2 dose (RP2D) level while dosing the least number of patients as possible at potentially sub-therapeutic doses. In the Phase 2 part of the study, preliminary efficacy will be evaluated in 6 expansion cohorts (total n = 60-136), using a Simon two-stage design. The RP2D will be selected based on the MTD, the safety profile, PK, and available pharmacodynamics data generated from all subjects in Phase 1.

In both Phase 1 and Phase 2, patients will be treated in continuous 28-day cycles and all patients will be assessed for response every 2 cycles. Treatment will be terminated if the patient progresses, cannot tolerate treatment, or withdraws consent from active therapy. Patients will undergo a safety evaluation approximately 1 month (28-35 days) after the last dose. Patients will be followed for response until progression is documented.

Clinical Study Identifier: NCT03997968

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