PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer
Status:
Active, not recruiting
Trial end date:
2027-07-15
Target enrollment:
Participant gender:
Summary
Of the approximately 21,000 cases of ovarian cancer diagnosed annually in the U.S, ten
percent are attributed to hereditary syndromes, most commonly the result of mutations in the
breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Mutation in these genes results
in the inability to repair double-stranded breaks in DNA. Treating these tumors with
poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors results in the specific
killing of BRCA negative cells by blocking a second DNA-repair mechanism. Treatment of
ovarian cancer patients with PARP inhibitors has resulted in improved progression free
survival (PFS), but not overall survival (OS). It's not completely understood why this is the
case, but some preclinical studies using ovarian cancer models in mice have suggested that
combining PARP inhibitors with immune system modulators like T cell checkpoint inhibitors
improves long-term survival.
Therefore, the purpose of this study is to evaluate the safety and efficacy of a combination
of a PARP inhibitor (Olaparib) with a T cell checkpoint inhibitor (the anti-CTLA-4 antibody
Tremelimumab) in women with recurrent BRCA mutation-associated ovarian cancer.