Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Pamela Munster
Photo of Pamela Munster
Pamela Munster

Description

Summary

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.

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

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.

Keywords

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 Oral RAD51-inhibitor; refractory; B-cell; solid tumor DNA Damage Repair inhibitor cancer Lymphoma Breast Neoplasms Neoplasms Sarcoma Lymphoma, Mantle-Cell Small Cell Lung Carcinoma Triple Negative Breast Neoplasms CYT-0851

Eligibility

For people ages 18 years and up

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:
  5. Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy
  6. Relapsed, refractory chronic lymphocytic leukemia requiring therapy
  7. Relapsed or progressive multiple myeloma on or after treatment
  8. Histologically-proven solid tumor meeting the following criteria:
  9. Metastatic breast cancer
  10. Recurrent squamous cell carcinoma of the head and neck
  11. Ovarian cancer
  12. Soft tissue sarcoma
  13. Recurrent metastatic or locally advanced pancreatic cancer
  14. 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:
  7. Triple negative breast cancer
  8. Ovarian cancer
  9. Pancreatic cancer
  10. Soft tissue sarcoma
  11. 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
  5. ANC < 1.0 x 109/L; PLT < 75 x 109/L; Hgb < 9.0 g/dL

  6. Calculated Creatinine clearance (Cockcroft-Gault) < 40 mL/min
  7. Hepatic function: AST > 2.0 x ULN; ALT > 2.0 x ULN;
  8. Total bilirubin > 1.5 x ULN;
  9. Albumin < 2.8 g/dL
  10. Screening QTc interval > 450 milliseconds (males) and > 470 ms for females

Locations

  • University of California San Francisco accepting new patients
    San Francisco California 94158 United States
  • Stanford Comprehensive Cancer Center accepting new patients
    Stanford California 94305 United States

Lead Scientist at UCSF

  • Pamela Munster
    Professor, Medicine. Authored (or co-authored) 131 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Cyteir Therapeutics, Inc.
ID
NCT03997968
Phase
Phase 1/2
Study Type
Interventional
Last Updated