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 as a monotherapy and in combination with chemotherapy for evaluation in these patients.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
Key Phase 1 Inclusion Criteria. 1. Male or female ≥18 years of age at time of informed consent. 1. Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative serum pregnancy test at most 30 days before enrollment and within 72 hours before the first administration of CYT-0851. 2. Female subjects of childbearing potential must not donate ova during the study and for at least 90 days after the last dose of study drug and must agree to continue using an effective method of contraception during the screening period to first study drug administration until 90 days after the last dose of study drug. 3. Male subjects who have not had a vasectomy must agree to use an effective method of contraception during the study and until 90 days after the last dose of the study drug, and to not donate sperm during the study and for at least 90 days after the last dose of study drug. 2. ECOG Performance Status of 0-1. 3. Measurable disease defined by disease-specific response criteria. 4. Histologically-proven B cell malignancies, meeting the following criteria: 1. Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy, after at least two prior therapies, and if transplanted, then at least 3-month post autologous stem cell transplant and if CART-treated, then evidence of progression no sooner than 3 months post CART treatment, or. 2. Relapsed, refractory chronic lymphocytic leukemia requiring therapy after at least two prior therapies, including BTK and BCL-2 inhibitor therapy (unless ineligible for such therapy), or. 3. For multiple myeloma, relapsed or progressive on or after treatment with at least three prior therapies that included a proteasome inhibitor, an imide, daratumumab, and if transplant eligible, a bone marrow transplant (unless unfit for transplant), or. 5. Histologically-proven solid tumor meeting the following criteria: 1. Patients must have failed, refused, or not be eligible for further standard therapies (including chemotherapy, hormonal therapies, Her-2 directed therapies, as appropriate) expected to provide clinical benefit, and meeting the following criteria. 2. Metastatic breast cancer (including ER/PR positive or negative, Her-2 positive and negative, triple negative), treated with at least 1 prior therapy for metastatic disease, or. 3. Recurrent squamous cell carcinoma of the head and neck (HNSCC) (dose escalation) or human papilloma virus positive (HPV+) HNSCC (dose-escalation and backfill), treated with at least 1 prior therapy, or. 4. Ovarian cancer, progressive after treatment with at least prior platinum-based chemotherapy, and therapy with a PARP inhibitor or. 5. Soft tissue sarcoma, treated with at least one line of prior systemic therapy, or. 6. Recurrent metastatic or locally advanced pancreatic cancer after first line chemotherapy (backfill patients only) or. 7. Histologically-proven advanced small-cell lung cancer (SCLC) (backfill patients only). 1. Patients with mixed histology are not allowed. 2. Prior treatment with platinum containing chemotherapy regimen with no evidence of progression within 90 days of last dose of platinum agent and anti-PD-(L)1 unless contraindicated. 3. At least 1 prior line of chemotherapy, but no more than 3 prior lines of therapy. 6. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure. 7. Willing and able to comply with the requirements of the study protocol. 8. Site of disease amenable to a biopsy and willing to undergo biopsy required for backfill, or for dose-escalation if considered unsafe (approval to participate in the study required by the Medical Monitor) provide an archival sample ≤ 12 months old. Key Phase 2 Inclusion Criteria. 1. Male or female ≥18 years of age at time of informed consent. 1. Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative serum pregnancy test at most 30 days before enrollment and within 72 hours before the first administration of CYT-0851. 2. Female subjects of childbearing potential must not donate ova during the study and for at least 90 days after the last dose of study drug and must agree to continue using, an effective method of contraception during the screening period to first study drug administration until 90 days after the last dose of study drug. 3. Male subjects who have not had a vasectomy must agree to use an effective method of contraception during the study and until 90 days after the last dose of the study drug, and to not donate sperm during the study and for at least 90 days after the last dose of study drug. 2. ECOG Performance Status of 0-1. 3. Measurable disease defined by disease-specific response criteria. 4. Site of disease amenable to a biopsy and willing to undergo a biopsy for the determination of biomarker status, or, if considered unsafe (approval to participate in the study required by the Medical Monitor), archival sample ≤ 12 months old for determination of biomarker status. 5. Biomarker positive on recent biopsy or bone marrow sample if required for the specific cohort. 6. Histologically-proven B cell malignancies, meeting the following criteria: 1. DLBCL Cohort. 1. Histologically-documented DLBCL or double hit lymphoma (B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma with BCL2 and MYC translocations (WHO Classification) 2. Progressing on or after treatment with at least two prior lines of therapy, including R-CHOP or equivalent first line therapy. 3. If transplanted, then at least 3-month post autologous stem cell transplant. 4. If CART-treated, then evidence of progression no sooner than 3 months post CART treatment. 2. MCL Cohort. 1. Histologically-documented MCL. 2. Any stage at diagnosis. 3. Progressing on or after treatment with at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor, after a 14-day washout period. 3. Multiple Myeloma Cohort 1) Relapsed or progressing after treatment with at least 3 prior therapies that include a proteasome inhibitor, an Immunomodulatory imide drug (IMiD), daratumumab, and, if transplant eligible, a bone marrow transplant (unless unfit for transplant) 7. Or Histologically-proven solid tumors meeting the following criterial. 1. Patients must have failed, refused, or not be eligible for further standard therapies (including chemotherapy, hormonal therapies, Her-2 directed therapies, as appropriate) expected to provide clinical benefit, and meeting the following criteria. 2. Triple Negative Breast Cancer Cohort. 1. Histologically-documented triple negative breast cancer, ER/PR negative (defined as <10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis), and HER2-negative, defined as either of the following by local laboratory assessment:
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03997968 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 1/Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Cyteir Therapeutics, Inc. |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Judson Englert, MD |
Principal Investigator Affiliation | Cyteir Therapeutics |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Recruiting |
Countries | United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
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 |
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.
Experimental: CYT-0851 dose escalation
Part A: CYT-0851 administered orally in rising doses QD or BID for 28 day cycles
Experimental: CYT-0851 dose expansion
Part B: CYT-0851 administered orally at the selected Phase 2 dose for 28 day cycles
Experimental: CYT-0851 and rituximab and bendamustine
Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab on Day 1 and bendamustine on Days 1 and 2 of each 28 day cycle
Experimental: CYT-0851 and gemcitabine
Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine on Day 1, 8 and 15 of each 28 day cycle
Experimental: CYT-0851 and capecitabine
Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine on Days to 14 of each 21 day cycle
Drug: - CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles
Drug: - CYT-0851 in combination with gemcitabine
Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine
Drug: - CYT-0851 in combination with capecitabine
Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine
Drug: - CYT-0851 in combination with rituximab and bendamustine
Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab and bendamustine
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
Mayo Clinic
Scottsdale, Arizona, 85259
Status
Recruiting
Address
University of California San Francisco
San Francisco, California, 94158
Status
Recruiting
Address
Stanford Comprehensive Cancer Center
Stanford, California, 94305
Status
Recruiting
Address
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Status
Recruiting
Address
Mayo Clinic
Jacksonville, Florida, 32224
Status
Recruiting
Address
Florida Cancer Specialists and Research Institute
Sarasota, Florida, 34232
Status
Recruiting
Address
Massachusetts General Hospital
Boston, Massachusetts, 02114
Status
Recruiting
Address
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Status
Recruiting
Address
University of Michigan
Ann Arbor, Michigan, 48109
Status
Recruiting
Address
Mayo Clinic
Rochester, Minnesota, 55905
Status
Recruiting
Address
John Theurer Cancer Center at HUMC
Hackensack, New Jersey, 07601
Status
Recruiting
Address
NYU Langone Health
New York, New York, 10016
Status
Recruiting
Address
Oklahoma University-Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Status
Recruiting
Address
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Status
Recruiting
Address
Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee, 37203
Status
Recruiting
Address
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Status
Recruiting
Address
University of Washington Seattle Cancer Center
Seattle, Washington, 98109
Status
Recruiting
Address
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226