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

Trial Status: Active

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.

Inclusion Criteria

  • ECOG Performance Status of 0-1
  • Measurable disease
  • Willing to undergo a tumor biopsy
  • 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
  • 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
  • Histologically-proven solid tumors:
  • Triple negative breast cancer
  • Ovarian cancer
  • Pancreatic cancer
  • Soft tissue sarcoma
  • Other biomarker positive cancers

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
  • 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

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE

New Jersey

Hackensack
Hackensack University Medical Center
Status: ACTIVE

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Cyteir Therapeutics, Inc.

  • Primary ID CYT-0851-01
  • Secondary IDs NCI-2019-06977
  • Clinicaltrials.gov ID NCT03997968