A Phase 1/2 Study of CYT-0851, an Oral RAD51 Inhibitor, in B-Cell Malignancies and Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03997968|
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : August 12, 2021
|Condition or disease||Intervention/treatment||Phase|
|Malignancy Non-hodgkin Lymphoma Multiple Myeloma Breast Cancer Ovarian Cancer Soft Tissue Sarcoma Head and Neck Cancer DLBCL Mantle Cell Lymphoma Follicular Lymphoma Pancreatic Cancer CLL Small Cell Lung Cancer Squamous Cell Carcinoma of Head and Neck Triple Negative Breast Cancer||Drug: CYT-0851||Phase 1 Phase 2|
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. Upon identification of the RP2D in the monotherapy, the study will open to three combination treatment arms to identify the RP2D in combination with rituximab and bendamustine in Non-Hodgkin Lymphoma and capecitabine or gemcitabine for solid tumors. 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 21-day or 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||320 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Center, Open Label Phase 1/2 Study of CYT-0851, an Oral RAD51 Inhibitor, in Patients With Relapsed/Refractory B-Cell Malignancies and Advanced Solid Tumors|
|Actual Study Start Date :||October 9, 2019|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||October 2022|
Experimental: Experimental: Active treatment
This is an open label study. All patients will receive single agent CYT-0851 administered orally or CYT-0851 in combination with chemotherapy.
Montherapy patients will receive CYT-0851 as a single agent
Combination arm patients will receive CYT-0851 in combination with chemotherapy
Other Name: Gemcitabine
Combination arm patients will receive CYT-0851 in combination with anti-CD20 antibody and chemotherapy
- Dose limiting Toxicity [ Time Frame: Phase 1: 12 months; ]Identify nature and frequency of dose limiting toxicities
- Overall Response Rate [ Time Frame: 24 Months ]Percent of Patients responding to treatment
- Adverse Events [ Time Frame: 24 months ]
- Evaluate the safety of CYT-0851
- Establish the PK of CYT-0851 Evaluate the type and frequency of adverse events
- Blood CYT-0851 concentrations [ Time Frame: Phase 1: 12 months ]Measure CYT-0851 concentrations over time
- Duration of Response [ Time Frame: 24 months ]For responders, time from response to progression
- Overall survival [ Time Frame: 24 months ]Time from treatment start to death
- Progression-free survival [ Time Frame: 24 months ]Time from treatment start to progression or death
- Laboratory and ECG abnormalities [ Time Frame: 24 months ]Percentage of grade of laboratory and ECG abnormalities
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997968
|Contact: Judson Englert, MDfirstname.lastname@example.org|
|Contact: Susan Dolemanemail@example.com|
|Study Director:||Judson Englert, MD||Cyteir Therapeutics|