|Clovis Oncology’s Rucaparib Demonstrates Encouraging Results from Ongoing Phase I/II Monotherapy Study in Patients with Solid Tumors|
“Oral rucaparib is a potent PARP inhibitor active in patients with
ovarian, breast and pancreatic cancers. Clinically meaningful results
have been seen in the rucaparib monotherapy Phase I trial; 89% of
patients with ovarian cancer demonstrated a clinical benefit. Increasing
evidence suggests that genetic analysis of ovarian tumors can help
identify patients who derive benefit from PARP inhibitor therapy – best
known predictors are mutations in BRCA genes, either at germline or
somatic level, but there are likely other predictive mutations as well.
The Clovis development program seeks to exploit these new insights and I
am pleased to be jointly leading their larger-scale trials to assess the
full clinical potential of this well-tolerated drug in ovarian cancer,”
“These initial results suggest that rucaparib is both well-tolerated and
predictably absorbed, and provides meaningful clinical benefit to
certain ovarian cancer patients,” said
The Phase I dose escalation portion of the study is open to patients with all solid tumors. Study objectives were typical for a Phase I trial, including determining safety and tolerability, evaluating the pharmacokinetic profile, identifying the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) as well as the preliminary efficacy signals in various solid tumors.
Thirty-seven patients have been treated with rucaparib monotherapy in
this study as of
Patients have received a median of four previous anticancer regimens and over half have received three or more previous therapies. Twenty-one patients (57%) have breast tumors, 10 patients (27%) have ovarian/peritoneal tumors and six patients (16%) have other solid tumors.
Key data from the study presented at
Evidence of Activity
Objective responses have been observed in ovarian, breast and pancreatic cancer patients with germline BRCA mutations. Durable disease control has been observed in heavily pre-treated ovarian cancer patients across all dose levels, with a disease control rate of 89% (stable disease or better beyond 12 weeks after study initiation in 8 of 9 ovarian cancer patients). The disease control rate for germline BRCA mutant ovarian cancer patients was 100% (7 of 7). Measurable disease was not a requirement for entry into the dose escalation phase of the study, precluding systematic response analysis.
Safety and Tolerability
Safety data to date shows rucaparib to be well-tolerated, which is important for a drug intended to be used in a maintenance setting. There were 19 patients (54%) with treatment-related adverse events. The most common adverse events attributed to rucaparib therapy include fatigue (23%), nausea (14%) and decreased appetite (11%). No patient experienced a treatment-related adverse event that led to study drug discontinuation and no grade 3/4 myelosuppression has been observed in any patient. There have been two treatment related grade 3 toxicities: one patient with grade 3 nausea and one patient with grade 3 fatigue.
Oral rucaparib has attractive pharmacokinetic properties as a potential oral cancer therapeutic. Patients receiving BID doses above 240 mg experienced consistently high plasma drug concentrations throughout the 24-hour period, which is likely important for optimal activity. Intra- and inter-patient variability was also low, which is advantageous for uniform flat dosing strategies.
The poster, titled “A Phase I Dose Escalation and Pharmacokinetic Study
of Continuous Oral Rucaparib in Patients with Advanced Solid Tumors,” is
being presented on
Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 in development for the treatment of ovarian cancer. Rucaparib is currently in two Company-sponsored Phase I clinical studies; one to determine the maximum tolerated dose (MTD) of oral rucaparib administered on a daily basis as monotherapy; and a second trial to determine the MTD of oral rucaparib that can be combined with intravenous platinum chemotherapy for the treatment of solid tumors. Once the optimal dose and schedule have been established in the Phase I portion of the monotherapy study, the Company will initiate a Phase II expansion cohort to assess efficacy in selected ovarian cancer patients. The Company expects to initiate a biomarker study in platinum-sensitive ovarian cancer patients in the third quarter of 2013, as well as the pivotal Phase III study in platinum-sensitive ovarian cancer patients in late 2013.
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