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Expanded Rubraca Data from Clovis Oncology's ARIEL3 and TRITON2 Trials in Ovarian and Prostate Cancers Presented at 2019 ASCO Annual Meeting.

M2 PHARMA-June 3, 2019-Expanded Rubraca Data from Clovis Oncology's ARIEL3 and TRITON2 Trials in Ovarian and Prostate Cancers Presented at 2019 ASCO Annual Meeting

(C)2019 M2 COMMUNICATIONS

- US-based Clovis Oncology, Inc. (NASDAQ: CLVS) is presenting multiple datasets at the 2019 American Society of Clinical Oncology annual meeting in Chicago, the company said.

These include presentations of exploratory endpoint evaluations and updated safety data from the pivotal Phase 3 ARIEL3 trial evaluating Rubraca (rucaparib) for the maintenance treatment of advanced ovarian cancer, as well as genomic characteristics of BRCA1/2 mutations among metastatic castration-resistant prostate cancer (mCRPC) patients in the Phase 2 TRITON2 trial evaluating Rubraca in mCRPC.

During an afternoon session on Saturday, June 1, Robert L. Coleman, MD, professor of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center in Houston and co-coordinating investigator in the ARIEL3 clinical trial programme, presented the poster "Exploratory analysis of the effect of maintenance rucaparib on post-progression outcomes in patients with platinum-sensitive recurrent ovarian carcinoma and updated safety data from the phase 3 study ARIEL3" (Abstract #5522/Poster Board #345).

Data from this analysis of the ARIEL3 trial, which enrolled patients with platinum-sensitive recurrent ovarian carcinoma, demonstrated that Rubraca significantly improved the clinically meaningful exploratory endpoints of chemotherapy-free interval, time to start of first subsequent therapy, time to investigator-assessed progression on the subsequent line of treatment or death, and time to second subsequent therapy vs. placebo.

The updated safety profile generated in this analysis is consistent with the previously-reported primary efficacy data analysis based on a data cutoff date of April 15, 2017.

As of December 31, 2017, the most common treatment-emergent adverse events (TEAEs) of any grade (rucaparib vs. placebo) were nausea (75.8% vs. 36.5%), asthenia/fatigue (70.7% vs. 44.4%), dysgeusia (39.8% vs. 6.9%), and anemia/decreased hemoglobin (39.0% vs. 5.3%).

The most common grade >=3 TEAEs were anemia/decreased hemoglobin (21.5% vs. 0.5%) and alanine/aspartate aminotransferase increase (10.2% vs. 0.0%).

Also on Saturday, June 1, Wassim Abida, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, and coordinating investigator for the TRITON2 study, presented the poster "Genomic characteristics of deleterious BRCA1 and BRCA2 alterations and associations with baseline clinical factors in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TRITON2" (Abstract #5031/Poster Board #143).

The ongoing phase 2 TRITON2 (NCT02952534) study is evaluating the poly(ADP-ribose) polymerase inhibitor rucaparib in mCRPC patients harboring a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or other DNA damage repair genes as determined by central screening of tumor tissue or plasma, or from local testing.

Next-generation sequencing assays evaluating tumor tissue and circulating cell-free tumor DNA (ctDNA) in plasma were both used to successfully identify patients with eligible alterations in BRCA1/2. The plasma assay is minimally invasive and reliably detects alterations in patients with disease that is difficult to biopsy.

In this analysis, associations between baseline genomic and clinical characteristics were assessed. Several findings support the hypothesis that germline BRCA1/2 alterations are a prognostic factor in prostate cancer associated with more rapid progression to advanced disease.

Patients with germline BRCA1/2 alterations were younger at time of enrollment into TRITON2, had more advanced disease at time of diagnosis and had a shorter time between diagnosis and enrollment into TRITON2 as compared to patients with somatic BRCA1/2 alterations.

However, responses to rucaparib were observed in patients with germline or somatic BRCA1/2 alterations, highlighting the potential of rucaparib to benefit both groups of patients.

This poster includes the confirmed objective response rate data based on the same June 29, 2018 visit cut-off date presented at ESMO 2018 and presents those data by germline or somatic BRCA1/2 mutation status.

By investigator-assessed RECIST/PCWG3, the confirmed ORR in patients with a germline or somatic BRCA1/2 mutation treated with Rubraca was 50% or 40%, respectively. By PSA response, the confirmed ORR in patients with a germline or somatic BRCA1/2 mutation treated with Rubraca was 66.7% (10/15) or 43.3% (13/30), respectively.

Two trials in progress posters describe investigator-initiated studies that were selected for poster presentations at the 2019 ASCO annual meeting.

These include a multi-center Phase 2 trial of rucaparib in combination with nivolumab as maintenance therapy for patients with advanced biliary tract cancer.

The ARIEL3 pivotal study of rucaparib is a confirmatory randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive ovarian cancer patients can extend the period of time for which the disease is controlled after a complete or partial response to platinum-based chemotherapy.

The study enrolled 564 patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer. To be eligible for the study, participants had to have received at least two prior platinum-based treatment regimens, been sensitive to the penultimate platinum regimen, and achieved a complete or partial response to their most recent platinum-based regimen.

There were no genomic selection criteria for this study. Trial participants were randomized 2: 1 to receive 600 milligrams of rucaparib twice daily or placebo.

The study achieved its primary endpoint of improved PFS by investigator review in each of three populations. PFS was also improved in the rucaparib group compared with placebo by independent review, a key secondary endpoint, in all three populations. In addition, rucaparib improved objective response rate vs. placebo among evaluable trial participants in all three study populations.

TRITON2 is an international, multicenter, open-label Phase 2 study of Rubraca in men with metastatic castration-resistant prostate cancer with BRCA gene alterations (inclusive of germline or somatic), which is also enrolling patients with deleterious alterations of other DNA damage repair genes, including ATM. The study is currently enrolling across sites worldwide. For more information, visit www.tritontrials.com.

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed medical product outside of the US and the EU.

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Date:Jun 3, 2019
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