Monday September 30, 2019 0 comments
BOULDER -- Clovis Oncology, Inc. (NASDAQ: CLVS) announced updated data from the Phase 2 TRITON2 trial at the European Society for Medical Oncology (ESMO) Congress 2019, reinforcing the potential of Rubraca® (rucaparib) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA1/2 mutation.
The company said its data shows a 43.9% confirmed objective response rate (ORR) by investigator assessment in 57 RECIST*/PCWG3** response-evaluable patients with a BRCA1/2 mutation.
When assessed by independent radiological review, the response rate was similar (40.4%). In addition, a 52.0% confirmed prostate-specific antigen (PSA) response rate was observed in 98 response-evaluable patients with a BRCA1/2 mutation.
Confirmed radiographic responses were durable, with 60 percent lasting 24 weeks or longer (15/25), the company said.
Clovis said the TRITON2 data will be used to support the filing of the company’s planned supplemental NDA to the Food and Drug Administration (FDA) for Rubraca in BRCA1/2-mutant advanced prostate cancer.
“The updated data from the TRITON2 trial confirm the potential role of rucaparib in treating metastatic castration-resistant prostate cancer,” said Wassim Abida, medical oncologist, Memorial Sloan Kettering Cancer Center, and principal investigator for the TRITON2 study.
“These data specifically demonstrate the efficacy of rucaparib in eligible mCRPC patients with a BRCA1/2 mutation and reinforce the known safety profile in this treatment setting, showing it has the potential to offer clinical benefit to eligible patients.”
Confirmed investigator-assessed RECIST* and PSA responses were also observed in patients with alterations in other DDR genes, including ATM, CDK12, CHEK2, PALB2, BRIP1, FANCA, and RAD51B, Clovis said.
The median duration of follow-up (as of July 2, 2019) for patients in TRITON2 was 13.1 months (range 4.1–28.5 months) with the safety profile consistent with prior reports.
The most common any-grade treatment-emergent adverse events (TEAE) >20% in the TRITON2 trial were asthenia/fatigue (55.3%), nausea (49.5%), anemia/decreased hemoglobin (37.9%), decreased appetite (27.9%), transient increased aspartate transaminase/alanine aminotransferase (ALT/AST) (24.7%), constipation (24.7%), vomiting (22.1%) and diarrhea (21.1%).
Clovis Oncology said it is further evaluating the potential of Rubraca to treat advanced prostate cancer in the TRITON3 clinical trial -- a multicenter, randomized, open-label Phase 3 study of Rubraca versus physician’s choice of therapy -- for patients with mCRPC.
TRITON3 is currently enrolling patients with BRCA1/2-mutant and ATM-mutant (both inclusive of germline and somatic) tumors with a primary objective of assessing radiographic progression-free survival (PFS) in these patients.
An exploratory data analysis from the pivotal Phase 3 ARIEL3 trial evaluating Rubraca for the maintenance treatment of recurrent ovarian cancer assessed PFS in the subgroups who had achieved a partial response (PR) or complete response (CR) on the most recent platinum regimen.
Clovis said the data shows PFS was longer in patients receiving Rubraca than placebo regardless of whether patients achieved a CR or PR on their last platinum-based regimen. Patients in the intent-to-treat population who received rucaparib treatment had a significantly greater reduction in risk for progression or death versus placebo.
“The ARIEL3 data presented at ESMO this year demonstrate that rucaparib contributes to a significant increase in progression-free survival over placebo, irrespective of whether a patient had CR or PR to previous platinum-based therapy and provides strong evidence for efficacy in women with recurrent ovarian cancer in the second-line maintenance setting,” said Jonathan Ledermann, professor of medical oncology, UCL Cancer Institute and UCL Hospitals, London, global principal Investigator for non-U.S. sites in the ARIEL3 study.
“The current data provide physicians with a compelling argument to make maintenance therapy essential for all eligible patients, including women who have had a complete response.”
Data from the Study 10, ARIEL2 and ARIEL3 trials supported the approvals of Rubraca for the treatment and maintenance treatment of recurrent ovarian cancer in the U.S. and EU, Clovis said.
The European Commission authorization of Rubraca, resulted in Rubraca being the first poly (ADP ribose) polymerase (PARP) inhibitor to be approved for both treatment and maintenance treatment among eligible women with ovarian cancer in the EU.
“Rubraca continues to demonstrate meaningful clinical benefit in the recurrent ovarian cancer treatment and maintenance settings, and our updated prostate data are highly consistent with the data presented at ESMO last year,” said Patrick J. Mahaffy, president and CEO of Clovis Oncology.
“We are moving forward with plans to file an sNDA in advanced mCRPC by the end of 2019, and we believe that, similar to its ovarian cancer profile, Rubraca may offer an important treatment option for patients with advanced prostate cancer, for whom new options are needed.
“We are committed to further exploring the potential of Rubraca and look forward to starting the tumor-agnostic study before year-end and furthering our combination studies that are now enrolling patients.”