A Phase II Study of Avelumab Immunotherapy and Talazoparib for Patients with Advanced Cancers that Have BRCA or ATM Mutations

Full Title

A Phase 2 Study to Evaluate Safety and Anti-Tumor Activity of Avelumab in Combination with Talazoparib in Patients with BRCA or ATM Mutant Tumors

Purpose

The purpose of this study is to assess the safety and effectiveness of combining two drugs, avelumab and talazoparib, to treat patients with advanced cancers that contain BRCA or ATM mutations and continue to grow despite standard therapy. Avelumab is a form of immunotherapy that works by blocking a protein on tumor cells called PD-L1. Tumor cells make PD-L1 to help them evade being detected by the immune system. By blocking this protein, avelumab may improve the ability of the immune system to find and destroy a cancer.

Talazoparib is a newer drug that stops the activity of a protein called PARP, which is involved in the repair of DNA damage. Some tumors with mutations in the BRCA1, BRCA2, or ATM genes depend on PARP for DNA repair while normal cells do not. This means that when talazoparib turns off PARP in cancer cells containing these mutations, the cancer cells may die. Some laboratory studies have shown that combining drugs that block PD-L1 and PARP may be more effective than using either drug by itself.

Avelumab is given intravenously (by vein) and talazoparib is taken orally (by mouth).

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have an advanced solid tumor containing one or more BRCA1, BRCA2, or ATM genetic mutations. Examples include ovarian cancer, breast cancer, metastatic castration-resistant prostate cancer, and pancreatic cancer.
  • Patients’ tumors must continue to grow despite prior therapy.
  • Patients should recover from the serious side effects of prior therapy before entering the study.
  • Previous treatment with a PARP inhibitor or checkpoint inhibitor is not allowed.
  • Patients must be physically well enough that they are fully ambulatory, capable of all self care, and are capable of all but physically strenuous activities. As an example, patients must be well enough that they would be able to carry out office work or light housework.
  • This study is for patients age 18 and older.

For more information about this study and to inquire about eligibility, please contact Dr. David Hyman at 646-888-4544.

Protocol

18-291

Phase

II

Disease Status

Relapsed or Refractory

Investigator

Co-Investigators