공시 • Sep 17
Clovis Oncology, Inc. Presents Highlight Breadth and Potential of Clovis Oncology Products and Pipeline At ESMO Virtual Congress 2020
Clovis Oncology, Inc. announced the data being presented as e-posters at the European Society for Medical Oncology Virtual Congress 2020. These include initial data from the Phase 1b part of the LIO-1 study of lucitanib in combination with Opdivo, new analyses of data from the pivotal Rubraca ARIEL3 and TRITON2 studies, initial data from the Phase 1b part of the SEASTAR study arm of Rubraca with Trodelvy™ (sacituzumab govitecan-hziy), and the first presentation of preclinical data for FAP-2286 Clovis’ novel peptide-targeted radionuclide therapy. Data presented from the Phase 1b part of the Phase 1b/2 LIO-1 study in patients with an advanced solid tumor (n=17) have identified the recommended starting Phase 2 dose of oral lucitanib to be used in combination with Opdivo and have shown promising signs of antitumor activity. The recommended oral starting dose of lucitanib was established as 6 mg once daily, to be given in combination with Opdivo at a fixed dose of 480 mg intravenously (IV) once every 28 days. Across three dose levels studied (6 mg, 8 mg and 10 mg) of oral lucitanib in combination with intravenous (IV) Opdivo at (480 mg once every 28 days), only one dose-limiting toxicity of Grade 3 proteinuria was observed among 17 patients, and there were no apparent differences in treatment-emergent adverse event (TEAE) frequencies between dose levels. In this small patient population, TEAEs were consistent with those expected for lucitanib and Opdivo. Grade 3 TEAEs included hypertension (n=4), diarrhea (n=1), and proteinuria (n=1); treatment-emergent hypertension was otherwise grade 1 or 2 (n=4), and readily managed with close monitoring and early hypertensive therapy. No grade =4 adverse events were reported. Given lucitanib’s relatively large inter-patient pharmacokinetic variability, a safety-based dose-titration approach is being used for the Phase 2 part of the study to optimize lucitanib efficacy as well as safety and tolerability. Among the 17 patients treated, 15 were evaluable for RECIST response as of the efficacy cut-off date: these include one patient with a confirmed complete response, one patient with a confirmed partial response, 10 patients have had a best response of stable disease and three patients had progressive disease. As of August 11, 2020, seven of the 17 patients remained on study, including the two responders and five of the patients with stable disease. In addition to data from the Phase 1b part of the LIO-1 study, a Trials in Progress (TiP) poster describing the study design of the Phase 2 part of LIO-1 was presented. The Phase 2 part of the study is currently enrolling patients to evaluate the efficacy and safety of the lucitanib and Opdivo combination in patients with advanced gynecological solid tumors, including ovarian, endometrial and cervical cancers. As described in the e-poster, a safety-based dose-titration approach is being used for lucitanib dosing to manage tolerability and maintain dose intensity. Investigators also presented new safety data analyses from the pivotal Rubraca studies ARIEL3 and pharmacokinetic (PK) analyses of TRITON2, providing additional information to healthcare professionals that can help support their ovarian and prostate cancer patients being treated with Rubraca. The ARIEL3 data presented in an e-poster reinforce the overall safety profile of Rubraca as a maintenance treatment in patients with recurrent ovarian cancer. After two years of additional follow up for those patients who continued on treatment in the study, the safety profile remains consistent with previous reports, with no new safety signals identified. As of the current safety data cutoff (December 31, 2019), 33 of 372 and 1 of 189 patients in the safety population were still receiving Rubraca or placebo, respectively. Median treatment duration was 8.3 months in the Rubraca arm and 5.5 months in the placebo arm. Prevalence of any-grade nausea declined progressively over the 24-month evaluation period, and prevalence of any-grade anemia/decreased hemoglobin peaked at month 4, decreasing to a plateau after month 8. The first onset of frequently reported TEAEs generally occurred early in treatment (=45 days). The median duration of the first event of frequently reported TEAEs was generally <60 days. Population pharmacokinetic (PK) analyses of 199 men with mCRPC receiving Rubraca in the TRITON2 study suggest there is no difference in Rubraca PK in men with mCRPC and women with ovarian cancer based on a comparison to a previously-developed model that used data from 454 women with ovarian cancer treated with Rubraca. The data in men with mCRPC show that differences among patients in the amount of Rubraca in the blood after administration of Rubraca at a dose of 600 mg twice daily did not appear to impact the efficacy of treatment. Also, a higher maximum concentration of Rubraca in the blood was not associated with increased rates of most safety endpoints analyzed, including hematologic adverse events. These PK data and exposure and safety/efficacy correlations using data from the TRITON2 study support the use of Rubraca in eligible mCRPC patients with a starting dose of 600 mg twice daily. TRITON2 served as the pivotal data supporting the May 2020 FDA approval of Rubraca as the first PARP inhibitor for patients with advanced mCRPC associated with a BRCA mutation. Investigators also presented in an e-poster initial data from the arm of the Phase 1b/2 SEASTAR study evaluating Rubraca in combination with Trodelvy in patients with advanced solid tumors (n=6). Data from the Phase 1b part of the study suggest encouraging initial antitumor activity for the novel combination, including patients with prior PARP inhibitor exposure and without a deleterious homologous recombination repair gene mutation. Despite early toxicities, including dose-limiting neutropenia in two of the three patients in the higher dose cohort, all six patients continued treatment for at least 12 weeks, with side effects effectively managed with dose modification and/or growth factor support. One patient remained on treatment as of the August 11, 2020 data cut-off date. All patients had a best response of stable disease or better, including three patients with a confirmed partial response (all three had been previously treated with a PARP inhibitor). And finally, the first data from a preclinical evaluation of FAP-2286, Clovis’ novel peptide-targeted radionuclide therapy to fibroblast activation protein (FAP) were presented in an e-poster. The data show that FAP-2286 potently and selectively binds FAP. FAP is highly expressed in cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and, in some cancers, its expression has also been observed in the tumor cells. Compelling anti-tumor activity was observed with 177Lu-FAP-2286 (Lutetium-177 conjugated to FAP-2286 for therapeutic use) in FAP-expressing tumor models.