A Phase 1/2 Study of CYT-0851, an Oral RAD51 Inhibitor, in B-Cell Malignancies and Advanced Solid Tumors
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 165
Summary
- Conditions
- Non Hodgkin Lymphoma
- Breast Cancer
- CLL
- DLBCL
- Follicular Lymphoma
- Triple -Negative Breast Cancer
- Soft Tissue Sarcoma
- Head and Neck Cancer
- Malignancy
- Mantle Cell Lymphoma
- Multiple Myeloma
- Small Cell Lung Cancer
- Squamous Cell Carcinoma of Head and Neck
- Ovarian Cancer
- Pancreatic Cancer
- Type
- Interventional
- Phase
- Phase 1Phase 2
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
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...
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 8 expansion cohorts (total n = 92-220), 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.
Tracking Information
- NCT #
- NCT03997968
- Collaborators
- Not Provided
- Investigators
- Study Director: Judson Englert, MD Cyteir Therapeutics