Demonstrated Anti-Tumor efficacy with rubraca

Demonstrated Anti-Tumor Efficacy with Rubraca—
44% of Patients Achieved a Response1

Confirmed objective response rate (ORR):
primary endpoint1*

  • ORR was defined per modified RECIST v1.1 criteria and with no confirmed bone progression per PCWG31
  • The ORR by IRR was similar in patients with germline vs somatic BRCA mutation1
  • Rapid response with Rubraca: of those that responded, the majority (70%) achieved an initial response by the first follow-up scan (week 8 visit)2
  • Six (9.7%) patients treated with Rubraca had disease progression2
  • One (1.6%) patient was not evaluable2

IRR-assessed response (N=62)

Bar chart of overall response rate (ORR) by IRR in Rubraca patients

Demonstrated Durability with Rubraca—
Several Responses Remained Ongoing at 2 Years1

Duration of response (DOR): secondary endpoint1*

  • The majority of patients (56%; 15/27) with a confirmed objective response had a DOR of ≥6 months1
  • Treatment with Rubraca was still ongoing in 44% (12/27) of patients at the time of data cut-off2
  • Median follow-up of 17.3 months2

IRR-assessed DOR

Rubraca: The First FDA-Approved
PARP Inhibitor in mCRPC1‡

TRITON2 includes the largest population of BRCAmut+ mCRPC patients evaluated on a PARP inhibitor

TRITON2

Multicenter, single-arm, phase 2 clinical trial3

mCRPC patients received prior AR-directed therapy and prior taxane chemotherapy2

Rubraca tablets 600 mg BID1

Continue until
disease progression
or
unacceptable toxicity1

Endpoints

Primary Endpoint

Objective response rate, ORR§

(assessed by independent radiologic review [IRR] and investigator)1

Secondary Endpoints

Duration of response, DOR

(assessed by IRR and investigator)1§

Prostate-cancer-specific antigen (PSA) response2

All patients received a concomitant GnRH analog or had prior bilateral orchiectomy.1

209

patients enrolled with HRD-positive mCRPC1,||

115

BRCAmut+ patients with measurable or nonmeasurable disease evaluated for efficacy and safety2,¶

62

patients with measurable disease at baseline by IRR1

Change in Prostate-Specific Antigen (PSA)
Levels From Baseline

Prostate-specific antigen (PSA): secondary endpoint1*

Change in PSA levels from baseline (N=115)*

55%

PSA50

More than half (55%; 95% CI: 45.2, 64.1) of patients with measurable or nonmeasureable disease had a PSA decrease from baseline of at least 50%1

PSA90

One in 5 patients
(21.7%; 95% CI: 14.6, 30.4) had a PSA decrease of
at least 90%1

Changes in PSA levels may be observed but have not been shown to correlate with clinical benefit or progression in individual patients treated with Rubraca

Efficacy was Evaluated in Patients With Advanced Age and Extensive Disease Burden (N=62)1,2

TRITON2 included a demographically diverse mCRPC patient population

Median age

73

years

(range, 52 to 88)1

Disease characteristics

Genetic characteristics

Germline/somatic BRCA mutation distribution1

Pie chart of germline/somatic BRCA mutation distribution in Rubraca patients

BRCA1/BRCA2 mutation distribution1

Pie chart of BRCA1/BRCA2 mutation distribution in Rubraca patients

Treatment history

Prior AR therapy1

100%

received at least 1 AR therapy

34%

received 2 prior AR therapies

2%

received 3+ prior AR therapies

Number of prior advanced prostate cancer therapies2**

2
52%
3
32%
4
11%
5
3%
>5
2%

Race Distribution; Black (10%), White (73%), Other (17%)

  • *
    ORR and DOR were assessed by blinded IRR and the investigator according to modified RECIST version 1.1/PCWG3 criteria.
  • †
    For a PSA50 and PSA90 response, respectively, the proportion of patients with a ≥50% decrease or a ≥90% decrease from baseline confirmed by a second consecutive measurement at least 3 weeks later; PSA measurements performed by local laboratory.
  • ‡
    FDA approval is contingent upon verification and description of clinical benefit in confirmatory trials.
  • §
    ORR and DOR were assessed in patients with measurable disease by blinded IRR and by the investigator according to modified RECIST v1.1/PCWG3 criteria.
  • ||
    Included patients with BRCA1/BRCA2, ATM, or molecular evidence of other homologous recombination deficiency.
  • All patients had a deleterious somatic or germline BRCA mutation detected from either central plasma, central tissue, or local testing.
  • **
    This includes HSPC and CRPC.
  • AR=androgen receptor-directed therapy; ATM=ataxia-telangiectasia mutated gene; BID=twice daily; BRCA=breast cancer susceptibility gene; BRCAmut+=BRCA-mutation positive; BRCAmut+ mCRPC=breast cancer susceptibility gene-positive metastatic castration-resistant prostate cancer; FDA=Food and Drug Administration; GnRH=gonadotropin-releasing hormone agonist; HRD=homologous recombination deficiency; HSPC=hormone sensitive prostate cancer; IRR=independent radiologic review; mCRPC=metastatic castration-resistant prostate cancer; PARP=poly(ADP-ribose) polymerase; PCWG3=Prostate Cancer Working Group 3; RECIST=Response Evaluation Criteria in Solid Tumors.

Labs & Safety

The majority of adverse reactions and lab abnormalities were mild to moderate (Grades 1 or 2)1

SEE LABS & SAFETY PROFILE

INDICATIONS

Rubraca is indicated:

Rubraca is 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. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

SELECT IMPORTANT SAFETY INFORMATION

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca.

Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Please see full Prescribing Information for additional Important Safety Information.

Reference: 1. Rubraca [prescribing information]. Boulder, CO; Clovis Oncology. 2. Data on file. Clovis Oncology; Boulder, CO. 3. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02952534. Accessed March 19, 2020.

INDICATIONS

Rubraca is indicated:

Rubraca is 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. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

SELECT IMPORTANT SAFETY INFORMATION

Read full ISI

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca.

Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Please see full Prescribing Information for additional Important Safety Information.

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