Clovis Oncology Initiates Rolling NDA Submission to the FDA for Rociletinib in the Treatment of Advanced EGFR-Mutant Non-small Cell Lung Cancer
Jul 1 15
Clovis Oncology, Inc. announced that it has commenced the submission of a New Drug Application (NDA) regulatory filing to the U.S. Food and Drug Administration (FDA) for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA approved test. Rociletinib is the Company’s novel, oral targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014. Clovis agreed with FDA that the submission would be a rolling NDA and has filed the first component for potential accelerated approval of rociletinib in the U.S. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. The Company intends to complete the NDA submission by late July 2015.
Clovis Oncology, Inc. Appoints Lindsey Rolfe as Chief Medical Officer and Executive Vice President of Clinical and Preclinical Development and Pharmacovigilance, Effective Early August 2015
Jun 22 15
Clovis Oncology, Inc. announced that Dr. Lindsey Rolfe, BSc, MB ChB, MRCP, FFPM, has been named Chief Medical Officer and Executive Vice President of Clinical and Preclinical Development and Pharmacovigilance, to become effective in early August 2015. Dr. Rolfe succeeds Dr. Andrew Allen, who will be stepping down from his role at Clovis at that time to create a new immuno-oncology focused biotechnology company and serve as its Chief Executive Officer. Dr. Rolfe joined Clovis in early 2010 and oversees rociletinib and rucaparib development in her current role as Senior Vice President of Clinical Development. Prior to her appointment as Executive VP and Chief Medical Officer, Dr. Rolfe served as Senior Vice President of Clinical Development at Clovis. Dr. Rolfe previously served in senior oncology development roles at Celgene Corporation, Pharmion Corporation, Cambridge Antibody Technology, UCB Inc. and Celltech Group plc. As Chief Medical Officer at Clovis, Dr. Rolfe will be responsible for clinical development, preclinical development, clinical operations and pharmacovigilance and will also serve on the Company’s executive committee. She will be based in the Company’s San Francisco office.
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.