RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated...for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Rucaparib is a treatment option for patients with mCRPC and a pathogenic BRCA1 and BRCA2 mutation (germline and/or somatic) who have been treated with androgen receptor-directed therapy and a taxane based chemotherapy.

At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 for both comparisons)....The duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a BRCA alteration.

OS maturity was 54% in the BRCA subgroup and 59% in the ITT population….Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations.

Clovis Oncology, Inc. (NASDAQ: CLVS) today announced positive top-line data from the Phase 3, open-label, multicenter, randomized TRITON3 trial demonstrating that Rubraca monotherapy treatment achieved the primary endpoint of significantly improved radiographic progression-free survival (rPFS)...Benefit was observed in both primary efficacy analyses of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): first, those who had mutations in BRCA, as well as all patients randomized in the trial, inclusive of mutations in BRCA or ATM (the overall intent-to-treat population (ITT)).

Clovis Oncology, Inc...today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for Rubraca (rucaparib) as a monotherapy treatment of adult patients with BRCA1/2-mutated mCRPC who have received at least one prior androgen receptor (AR)-directed therapy and taxane-based chemotherapy.

...- Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency...

...- Have a deleterious mutation in a BRCA1/2 or ATM gene...

...- Presence of pathogenic or likely pathogenic germline mutation/variant in BRCA2, BRCA1, ATM or PALB2 -...

...- Have a deleterious mutation (germline or somatic) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B....

RITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy....ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35-57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40-100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5-57%).

12 pts were enrolled, 7 with BRCA1/2 and 5 with CHEK2 muts. The confirmed PSA50 response rate to rucaparib was 41.7% (N=5/12, 95% CI: 19.3-68.1%)...In pts with measurable disease, the ORR was 60% (N=3/5, all with BRCA2). Median rPFS on rucaparib was 10.3 months (95% CI: 4.0 mo - NR)....Rucaparib can induce clinical responses in a biomarker-selected PCa population without concurrent ADT.

Results from TRITON2 showed antitumor activity for rucaparib in patients with BRCA+ mCRPC associated with or without co-occurring alterations in TP53.

...rucaparib showed a benefit in terms of PSA response rate and ORR in patients with BRCA2 and BRCA1 mutation in a phase-II study.

Confirmed objective response rate (ORR) in BRCA pts (with investigator-assessed measurable disease) and PSA response rates (in pts with and without measurable disease) are shown in the Table....Responses were observed in patients with germline or somatic alterations in BRCA1 or BRCA2.

Of patients with a BRCA1/2 alteration and measurable disease at baseline, 44.0% (11/25) had a confirmed objective response by investigator assessment (Table 2; Figure 4)

ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration….Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration...