Clovis Oncology Announces Updated Phase 2 Results from Two Ongoing Clinical Studies with Rucaparib: ARIEL2 and Study 10
May 30 15
Clovis Oncology announced updated Phase 2 results from two ongoing clinical studies with rucaparib: ARIEL2 and Study 10. Rucaparib is the Company’s investigational oral, potent, small molecule inhibitor of PARP1 and PARP2 being developed for the treatment of advanced ovarian cancer, specifically in patients with BRCA mutations and other DNA repair deficiencies beyond BRCA, commonly referred to as “BRCA-like.” To see the encouraging progression-free survival rates mirror the impressive response rates in both the BRCA-mutant and BRCA-like populations represents a very exciting step forward in the treatment of advanced ovarian cancer. Study objectives of the ARIEL2 trial include determining rucaparib activity in prospectively defined molecular subgroups through the assessment of PFS in patients with tumors that have germline and somatic BRCA mutations, those with a BRCA-like signature (patients whose tumors have DNA repair deficiencies that behave like BRCA mutations, but with normal BRCA genes), and patients whose tumors are biomarker negative. ORR, safety and pharmacokinetics are also analyzed. At the time of analysis, patients in the study had received a median of one prior treatment regimen and one prior platinum-based therapy regimen. Patients were treated with the recommended Phase 2 dose (RP2D) of 600mg twice daily (BID). Data from the ARIEL2 study of 204 patients show compelling clinical activity, including the first presentation of PFS for each subgroup followed in the study. A median PFS of 9.4 months in BRCA-mutant patients and a median of 7.1 months in patients with a BRCA-like signature were observed, compared to biomarker negative patients, in which median PFS was 3.7 months. Importantly, results from ARIEL2 demonstrate that tumor HRD analysis can identify a broader range of patients who may benefit from rucaparib therapy. 45% (33/74) of patients with the pre-specified BRCA-like signature achieved a RECIST and/or CA-125 response, and 30% (22/74) achieved a RECIST response. Responses were durable with 17 of 22 responders still ongoing at time of analysis. A 73% DCR was also observed. As expected, activity was limited in biomarker negative patients, 21% (13/62) of patients achieved a RECIST and/or CA-125 response and 13% (8/62) achieved a RECIST response. A 39% DCR was also observed. Data presented demonstrate that rucaparib is well tolerated with a manageable safety profile. The most common treatment-related AEs reported in =15% of all patients included nausea, asthenia/fatigue and transient ALT/AST elevations. These events were mostly Grade 1/2. The most common Grade 3/4 treatment-related AEs were anemia/decreased hemoglobin (16%) and transient ALT/AST elevations (11%). Study 10 Data in Platinum-Sensitive Germline BRCA-mutant Patients. Data from a second Phase 2 study of rucaparib in ovarian cancer were presented in a poster presentation and poster discussion session. The Phase 2 portion of Study 10, the initial dose finding study of rucaparib, was expanded to enroll 41 patients with relapsed, high-grade platinum-sensitive ovarian cancer associated with a deleterious germline BRCA mutation. These patients had all received 2-4 prior treatment regimens, and had a progression-free interval of six months or greater after their most recent platinum regimen. Patients were treated with the recommended Phase 2 dose of 600mg BID. Consistent with the ARIEL2 data in BRCA-mutant patients, a robust ORR was observed in this patient population. In 35 patients evaluable for activity, 74% (26/35) of patients achieved a RECIST and/or CA-125 response, and 66% (23/35) achieved a RECIST response; a 77% disease control rate (DCR) was observed. Robust activity was observed regardless of type of BRCA mutation, length of progression-free interval between platinum therapies and number of prior treatments: response rates (RECIST and CA-125) ranged from 72% to 80% in those categories, or 61% to 78% for RECIST alone. Responses to rucaparib were durable: 15 of 23 responses were still ongoing at time of analysis with a median duration of response of over 11 months. Importantly, 77% of patients treated with at least 3 lines of chemotherapy achieved a RECIST and/or CA-125 response, and 69% achieved a RECIST response. This is the subject population of the ongoing ARIEL2 Extension registration study. Rucaparib was well tolerated with a manageable safety profile; the most common AEs were fatigue/asthenia, nausea and anemia. Any Grade 3/4 AEs were successfully managed with dose modification. No patients discontinued due to treatment-related adverse events. ARIEL Pivotal Study Program: The ARIEL (Assessment of Rucaparib in Ovarian Cancer Trial) program is a novel, integrated translational-clinical program designed to accurately and prospectively identify patients with tumor genotypes associated with benefit from rucaparib therapy. The global ARIEL2 study, initiated in fourth quarter of 2013, has completed enrollment of approximately 200 ovarian cancer patients with relapsed, platinum-sensitive disease. ARIEL2 is a two-part single-arm open label study. Part 1 is in platinum-sensitive patients designed to identify pre-specified tumor characteristics that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient’s tumor and provisional results are described above. Part 2, referred to as the ARIEL2 Extension, is enrolling advanced ovarian cancer patients who have received at least three prior chemotherapy regimens and will evaluate clinical response in patients classified into molecularly-defined subgroups, including germline BRCA-mutant, somatic BRCA mutant and the BRCA-like signature, by a prospectively defined genomic signature. The Phase 2 portion of Study 10, the initial dose finding study, has been expanded to enroll an additional 40 patients with relapsed, high-grade ovarian cancer associated with a deleterious BRCA mutation (germline or somatic) and who received =3 prior chemotherapy regimens. The ARIEL3 pivotal study is a randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance therapy to platinum-sensitive patients can extend the period of time for which the disease is controlled after a positive outcome with platinum-based chemotherapy. Patients are randomized to receive either placebo or rucaparib and the primary endpoint of the study is PFS. The primary efficacy analysis will evaluate, in a step-down process, BRCA-mutant patients, all patients with a BRCA-like signature (including BRCA and non-BRCA), and then all patients. In addition to the ARIEL program in ovarian cancer, the Company is exploring rucaparib in other solid tumor types with significant BRCA and BRCA-like populations.
Clovis Oncology, Inc. Announces Consolidated Earnings Results for the First Quarter Ended March 31, 2015
May 6 15
Clovis Oncology, Inc. announced consolidated earnings results for the first quarter ended March 31, 2015. The company reported no revenues for the first quarter of 2015, compared to $13.6 million for the first quarter of 2014 which consisted of a milestone payment pursuant to its collaboration and license agreement for lucitanib with Les Laboratoires Servier (Servier), earned as a result of the expiration of the opposition period of a lucitanib European patent. Net loss attributable to common shareholders was $63.1 million, or $1.86 per share, for the first quarter of 2015 compared to a net loss of $30.7 million, or $0.91 per share, for the first quarter of 2014. Net loss for the first quarter of 2015 included share-based compensation expense of $8.7 million compared to $4.9 million for the first quarter of 2014. Operating loss was $64,225,000 against $28,483,000 a year ago. Loss before income taxes was $63,042,000 against $28,589,000 a year ago. The increase in net loss was primarily due to increased investment in research and development activities in 2015 as well as the lack of milestone revenue in 2015 as compared to 2014. Net cash burn for the first quarter of 2015 was $49.3 million.
Clovis Oncology, Inc. to Report Q1, 2015 Results on May 06, 2015
Apr 23 15
Clovis Oncology, Inc. announced that they will report Q1, 2015 results at 4:30 PM, US Eastern Standard Time on May 06, 2015