Clinical Trials

Date: 2016-12-08

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 2017 San Antonio Breast Cancer Symposium

Company: Medivation (USA - CA), now Pfizer (USA - NY)

Product: talazoparib (BMN 673)

Action mechanism:

• enzyme inhibitor/poly ADP ribose polymerase PARP inhibitor/PARP inhibitor. Talazoparib is a potent and specific inhibitor of PARP 1 and 2 that is being developed by Medivation for the treatment of selected solid tumors. In pre-clinical studies, talazoparib has shown single-agent anti-tumor activity, as well as synergy in combination with lowered doses of DNA-damaging agents, due to its dual mechanisms of cytotoxicity, PARP trapping, and inhibition of PARP enzyme activity. Trapping of PARP on DNA impairs DNA replication resulting in tumor cell death.

 

Disease: metastatic breast cancer

Therapeutic area: Cancer - Oncology

Country: Australia, Belgium, Brazil, France, Germany, Ireland, Israel, Italy, Republic of Korea, Poland, Russian Federation, Spain, Taiwan, Ukraine, UK, USA

Trial details:

• The Phase 3 EMBRACA trial is an open-label, 2:1 randomized, parallel, two-arm study of talazoparib as compared to the protocol specified physicians' choice of chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in gBRCA-mutated locally advanced and/or metastatic breast cancer patients who have received prior chemotherapy for their metastatic disease. The study is enrolling up to 430 patients. The primary objective of the study is to compare PFS of patients treated with talazoparib as a monotherapy relative to those treated with protocol-specified physicians' choice. (NCT01945775)

Latest news:

• • On December 8, 2017, Pfizer announced that the Phase 3 EMBRACA trial in patients with germline (inherited) BRCA1/2-positive (gBRCA+) locally advanced and/or metastatic breast cancer (MBC) demonstrated superior progression-free survival (PFS) in patients treated with talazoparib, compared to patients who received physician’s choice standard of care chemotherapy. The data have been presented as an oral presentation at the 2017 San Antonio Breast Cancer Symposium.
• Median PFS was 8.6 months (95% CI: 7.2, 9.3) for patients treated with talazoparib and 5.6 months (95% CI: 4.2, 6.7) for those treated with chemotherapy [HR: 0.54 (95% CI: 0.41, 0.71), p<0.0001]. This represents a 46% reduction in the risk of disease progression. In addition, the proportion of patients achieving a complete or partial response (objective response rate) in the talazoparib group was more than twice that of the control arm (62.6% for talazoparib vs. 27.2% for chemotherapy [OR: 4.99 (95% CI: 2.9-8.8), p<0.0001]).
• The results of the EMBRACA trial also showed that the PFS benefit with talazoparib was consistent across prespecified subgroups, including hormone receptor (HR) status (triple negative [TNBC] or hormone receptor-positive [HR+]), BRCA mutation (1 or 2), prior chemotherapy (whether patients had none or up to three chemotherapies before talazoparib), and history of central nervous system (CNS) metastases. There also was a statistically significant delay in the time to clinically meaningful deterioration in global health status/quality of life with talazoparib versus chemotherapy (HR 0.38 [95% CI 0.26-0.55], p<0.0001), as measured by the EORTC QLQ-C30, a cancer-specific, patient-reported quality of life questionnaire.
• Adverse events (AEs) observed with talazoparib were consistent with findings from previous trials. The most common AEs observed with talazoparib (any grade in at least 15% of patients) were anemia (52.8%), fatigue (50.3%), nausea (48.6%), neutropenia (34.6%), headache (32.5%), thrombocytopenia (26.9%), alopecia (25.2%), vomiting (24.8%), diarrhea (22%), constipation (22%), decreased appetite (21.3%), back pain (21%) and dyspnea (17.5%). The incidence of serious AEs was 31.8% in the talazoparib arm and 29.4% in the chemotherapy arm. Discontinuations due to AEs occurred in 7.7% of patients in the talazoparib arm and 9.5% of patients in the chemotherapy arm.
• In addition to EMBRACA, talazoparib demonstrated promising activity in patients with gBRCA+ MBC in the Phase 2 ABRAZO trial. Patients in ABRAZO had either been previously treated with platinum-based chemotherapy or were heavily pretreated with at least three prior lines of non-platinum-based chemotherapy.
• • On September 11, 2013, a Phase 3 trial sponsored by Medivation was published on the NIH website ClinicalTrials.gov for talazoparib and is currently recruiting participants.

Is general: Yes