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 |
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Recruitment Status :
Recruiting
First Posted : June 25, 2019
Last Update Posted : February 2, 2021
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| 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. 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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 280 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Experimental: Active treatment
This is an open label study. All patients will receive single agent CYT-0851 administered orally.
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Drug: CYT-0851
All patients will receive CYT-0851 as a single agent |
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Phase 1 Inclusion Criteria
- ECOG Performance Status of 0-1
- Measurable disease
- Willing to undergo a tumor biopsy
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Histologically-proven B cell malignancies, meeting the following criteria:
- Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy
- Relapsed, refractory chronic lymphocytic leukemia requiring therapy
- Relapsed or progressive multiple myeloma on or after treatment
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Histologically-proven solid tumor meeting the following criteria:
- Metastatic breast cancer
- Recurrent squamous cell carcinoma of the head and neck
- Ovarian cancer
- Soft tissue sarcoma
- Recurrent metastatic or locally advanced pancreatic cancer
- Advanced small-cell lung cancer
Key Phase 2 Inclusion Criteria
- ECOG Performance Status of 0-1
- Measurable disease defined by disease-specific response criteria
- Site of disease amenable to a biopsy and willing to undergo a biopsy
- Biomarker positive on recent biopsy or bone marrow sample if required
- Histologically-proven B cell malignancies, meeting the following criteria: DLBCL, MCL, or Multiple Myeloma requiring therapy
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Histologically-proven solid tumors:
- Triple negative breast cancer
- Ovarian cancer
- Pancreatic cancer
- Soft tissue sarcoma
- Other biomarker positive cancers
Key Exclusion Criteria
- Known active brain metastases
- Known history of meningeal involvement or meningeal carcinomatosis
- Spinal cord compression not definitively treated with surgery and/or radiation
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Laboratory assessments
- ANC < 1.0 x 10^9/L; PLT < 75 x 10^9/L; Hgb < 9.0 g/dL
- Calculated Creatinine clearance (Cockcroft-Gault) < 40 mL/min
- Hepatic function: AST > 2.0 x ULN; ALT > 2.0 x ULN;
- Total bilirubin > 1.5 x ULN;
- Albumin < 2.8 g/dL
- Screening QTc interval > 450 milliseconds (males) and > 470 ms for females
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, MD | 857-285-4140 | clinicaltrials@cyteir.com | |
| Contact: Susan Doleman | 857-285-4140 | clinicaloperations@cyteir.com |
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| Study Director: | Judson Englert, MD | Cyteir Therapeutics |
| Responsible Party: | Cyteir Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT03997968 |
| Other Study ID Numbers: |
CYT-0851-01 |
| First Posted: | June 25, 2019 Key Record Dates |
| Last Update Posted: | February 2, 2021 |
| Last Verified: | January 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Oral RAD51-inhibitor; refractory; B-cell; solid tumor DNA Damage Repair inhibitor cancer |
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Lymphoma Breast Neoplasms Multiple Myeloma Neoplasms Sarcoma Lymphoma, Mantle-Cell Small Cell Lung Carcinoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms by Site |
Breast Diseases Skin Diseases Carcinoma, Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoma, Non-Hodgkin Neoplasms, Connective and Soft Tissue |