Ben Schwartz is Associate Editor, Contemporary OB/GYN.
Other pipeline developments include a new company formed to develop OAB treatments, a phase III urothelial cancer study meeting its primary endpoint, the formation of a partnership to study RCC treatment, and more.
Phase IIb study begins for intraprostatic localized PCa drug
The first patient in a phase IIb study evaluating the safety and tolerability of PRX302 (topsalysin) has been dosed, according to Sophiris Bio Inc. The drug, which will be used to treat clinically significant localized prostate cancer, is a pore-forming protein engineered to be activated only in the presence of enzymatically active PSA. The phase IIb study will continue the work of the phase IIa proof-of-concept study that demonstrated that a targeted intraprostatic administration of PRX302 has the potential to safely ablate tumor cells in the prostate. The phase IIb multicenter, open-label study will enroll approximately 40 patients throughout the United States and United Kingdom. Safety and tolerability will be assessed post-treatment over 26 weeks. The study allows enrolled patients the option to retreat with a second dose of PRX302, with a larger biopsy to occur 6 months after the second dose. To be eligible for the retreatment, the patient cannot have experienced a significant adverse response attributable to the drug and the patient will need to have had a clinical response from the first dose but still have a clinical significant lesion area. Data for all patients is expected by the fourth quarter of 2018, and data from patients who did not receive the second retreatment is expected to be available by the first quarter of 2018.
Protocol amended for phase III trial of CRPC agent
Astellas Pharma Inc. and Pfizer Inc. have amended the protocol for the PROSPER trial, a phase III, multinational, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of enzalutamide (XTANDI) in patients with non-metastatic castration-resistant prostate cancer (CRPC). While the primary endpoint, metastasis-free survival, remains the same, the main purpose of the amendment is to revise the plan for analyses of the primary and secondary endpoints. This reduces the target sample size from 1,560 patients to approximately 1,440 patients. It also allows for quicker results from the study with an anticipated disclosure later this year instead of the original disclosure date of June 2019. Enzalutamide is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within tumor cells.
Company formed to develop agents for OAB, other conditions
Roivant Sciences has formed Urovant Sciences, a new company focused on developing treatments for urologic conditions. The company’s lead therapeutic candidate is vibegron, an oral ß3-adrenergic agonist being studied for overactive bladder. A completed randomized, placebo- and active comparator-controlled phase III study that enrolled over 1,000 patients conducted outside of the United States met its primary and key secondary endpoints. Urovant plans to initiate a multinational phase III registration program for vibegron in 2017.
Phase III urothelial cancer trial meets primary endpoint
Eli Lilly and Co. has announced that its phase III RANGE study of ramucirumab (Cyramza), a drug being investigated for the treatment of urothelial cancer, has met its primary endpoint of progression-free survival (PFS). The phase III global, randomized, double-blind, placebo-controlled trial is evaluating ramucirumab in combination with docetaxel in patients with locally advanced or unresectable or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy. This the first phase III study to show superior PFS over chemotherapy in a post-platinum setting in urothelial cancer, and ramucirumab is the first antiangiogenic agent to extend PFS in a phase III trial, Lilly said. The safety profile remains unchanged as the analysis was consistent with previous observations of ramucirumab. Grade ≥3 adverse events occurring at a rate of 5% or greater and that were higher on the ramucirumab-plus-docetaxel arm versus the placebo-plus-docetaxel arm were neutropenia, febrile neutropenia and hypertension. Lilly anticipates that, while the primary endpoint has been met, overall survival results will likely be required for global regulatory submission, and these results are expected in mid-2018.
NDA submitted for new formulation of mCRPC agent
Churchill Pharmaceuticals, LLC has submitted a new drug application to the FDA for abiraterone acetate (YONSA). YONSA is an improved ultramicrosize formulation of abiraterone to treat metastatic castration-resistant prostate cancer in combination with methylprednisolone, the company said. The NDA submission is based on the final results of the STAAR Study, a randomized, open-label trial that compared YONSA plus methylprednisolone, to Zytiga, another abiraterone formulation, plus prednisone in metastatic castration-resistant prostate cancer patients. A previous study of healthy volunteers also found that a 500-mg dose of Yonsa was found to be bioequivalent to a 1,000-mg dose of Zytga.
Partnership formed to conduct study of RCC treatment
Xynomic Pharma and the University of California, San Francisco (UCSF) have formed a strategic partnership to conduct PAX Study, a multinational, multicenter, randomized phase II/III study comparing pazopanib plus abexinostat against pazopanib monotherapy in patients with locally advanced or metastatic renal cell carcinoma. The study will be led by UCSF and will use data from a completed phase Ib study of pazopanib and abexinostat. The phase Ib study gathered data from 51 heavily pre-treated patients with metastatic solid tumors who were treated with pazopanib and abexinostat. Researchers observed durable tumor regressions in 70% of patients with pazopanib-refractory disease. Both Xynomic and UCSF view the partnership as a way to help accelerate the timeline for abexinostat for development and to ultimately receive regulatory approval in the U.S. and elsewhere.
Phase II RCC study to test immunotherapy combinations
A new nationwide, multi-site phase II study of renal cell carcinoma, called FRACTION-RCC, will test whether combining nivolumab with other investigational immunotherapy agents is more effective than the commonly used drug combination of nivolumab plus ipilimumab. Patients over age 18 years who have been diagnosed with renal cell carcinoma that has metastasized can be considered potential candidates for the study.
Phase II data for nonmuscle-invasive bladder Ca agent released
Cold Genesys Inc. has reported interim clinical data from a phase II trial evaluating, an oncolytic virotherapy to treat patients with BCG-unresponsive nonmuscle-invasive bladder cancer. A total of 45 of the 67 enrolled patients had evaluable 6-month data in the ongoing clinical trial. Overall 6-month complete response (CR) was 46.7%. The carcinoma in situ (CIS) only group contained 14 CRs (58.3%), the CIS with Ta or T1 group contained four CRs (33.3%) and the Ta/T1 group contained three CRs (33.3%). CG0070 is designed to replicate inside tumor cells, causing cell lysis and immunogenic cell death. The ruptured cancer cells can also release tumor-derived antigens. Long-term follow-up data will be provided near the end of 2017, according to Cold Genesys.