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

Study Purpose

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.

Recruitment Criteria

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
More Inclusion & Exclusion Criteria

Key Phase 1 Inclusion Criteria. 1. ECOG Performance Status of 0-1. 2. Measurable disease. 3. Willing to undergo a tumor biopsy. 4. Histologically-proven B cell malignancies, meeting the following criteria: 1. Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy. 2. Relapsed, refractory chronic lymphocytic leukemia requiring therapy. 3. Relapsed or progressive multiple myeloma on or after treatment. 5. Histologically-proven solid tumor meeting the following criteria: 1. Metastatic breast cancer. 2. Recurrent squamous cell carcinoma of the head and neck. 3. Ovarian cancer. 4. Soft tissue sarcoma. 5. Recurrent metastatic or locally advanced pancreatic cancer. 6. Advanced small-cell lung cancer. Key Phase 2 Inclusion Criteria. 1. ECOG Performance Status of 0-1. 2. Measurable disease defined by disease-specific response criteria. 3. Site of disease amenable to a biopsy and willing to undergo a biopsy. 4. Biomarker positive on recent biopsy or bone marrow sample if required. 5. Histologically-proven B cell malignancies, meeting the following criteria: DLBCL, MCL, or Multiple Myeloma requiring therapy. 6. Histologically-proven solid tumors: 1. Triple negative breast cancer. 2. Ovarian cancer. 3. Pancreatic cancer. 4. Soft tissue sarcoma. 5. Other biomarker positive cancers. Key Exclusion Criteria. 1. Known active brain metastases. 2. Known history of meningeal involvement or meningeal carcinomatosis. 3. Spinal cord compression not definitively treated with surgery and/or radiation. 4. Laboratory assessments. 1. ANC < 1.0 x 10^9/L; PLT < 75 x 10^9/L; Hgb < 9.0 g/dL. 2. Calculated Creatinine clearance (Cockcroft-Gault) < 40 mL/min. 3. Hepatic function: AST > 2.0 x ULN; ALT > 2.0 x ULN; 4. Total bilirubin > 1.5 x ULN; 5. Albumin < 2.8 g/dL. 5. Screening QTc interval > 450 milliseconds (males) and > 470 ms for females

Trial Details

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
Additional Details

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.

Arms & Interventions

Arms

Experimental: Experimental: Active treatment

This is an open label study. All patients will receive single agent CYT-0851 administered orally.

Interventions

Drug: - CYT-0851

All patients will receive CYT-0851 as a single agent

Contact a Trial Team

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.

Mayo Clinic, Scottsdale, Arizona

Status

Recruiting

Address

Mayo Clinic

Scottsdale, Arizona, 85259

Site Contact

Clinical Trials Referral Office

clinicaltrials@cyteir.com

855-776-0015

University of California San Francisco, San Francisco, California

Status

Recruiting

Address

University of California San Francisco

San Francisco, California, 94158

Site Contact

Lauren Wilch

Lauren.Wilch@ucsf.edu

415-353-3642

Stanford Comprehensive Cancer Center, Stanford, California

Status

Recruiting

Address

Stanford Comprehensive Cancer Center

Stanford, California, 94305

Site Contact

Mariel Rojas

mlrojas@stanford.edu

650-723-0530

Denver, Colorado

Status

Recruiting

Address

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

Site Contact

Susan Hall

Susan.Hall3@sarahcannon.com

720-754-2610

Mayo Clinic, Jacksonville, Florida

Status

Recruiting

Address

Mayo Clinic

Jacksonville, Florida, 32224

Site Contact

Clinical Trials Referral Office

clinicaltrials@cyteir.com

855-776-0015

Sarasota, Florida

Status

Recruiting

Address

Florida Cancer Specialists and Research Institute

Sarasota, Florida, 34232

Site Contact

Karolyn Simpson, RN

KaSimpson@flcancer.com

941-377-9993

Massachusetts General Hospital, Boston, Massachusetts

Status

Recruiting

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Site Contact

Dejan Juric, MD

djuric@partners.org

617-724-4000

Dana Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

University of Michigan, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan

Ann Arbor, Michigan, 48109

Site Contact

Monica Burness, MD

mburness@med.umich.edu

734-232-0759

Mayo Clinic, Rochester, Minnesota

Status

Recruiting

Address

Mayo Clinic

Rochester, Minnesota, 55905

Site Contact

Clinical Trials Referral Office

clinicaltrials@cyteir.com

855-776-0015

John Theurer Cancer Center at HUMC, Hackensack, New Jersey

Status

Recruiting

Address

John Theurer Cancer Center at HUMC

Hackensack, New Jersey, 07601

NYU Langone Health, New York, New York

Status

Recruiting

Address

NYU Langone Health

New York, New York, 10016

Site Contact

Nina Beri, MD

Nina.Beri@nyulangone.org

212-731-5770

Oklahoma City, Oklahoma

Status

Recruiting

Address

Oklahoma University-Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

Philadelphia, Pennsylvania

Status

Recruiting

Address

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

Site Contact

Dennis Stone

Dennis.Stone@Jefferson.edu

215-955-6407

Nashville, Tennessee

Status

Recruiting

Address

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203

Site Contact

Davinia McComb, RN, OCN

clinicaltrials@cyteir.com

615-815-9963

Houston, Texas

Status

Recruiting

Address

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Site Contact

Sarah Travasos

sktravasos@mdanderson.org

713-563-4431

Seattle, Washington

Status

Recruiting

Address

University of Washington Seattle Cancer Center

Seattle, Washington, 98109

Site Contact

Harini Ramachandran

harinir@seattlecca.org

206-606-6448

Medical College of Wisconsin, Milwaukee, Wisconsin

Status

Recruiting

Address

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Site Contact

Michael Jacklin

mjacklin@mcw.com

414-804-8839