Other pipeline products discussed in this round-up include agents for metastatic urothelial cancer, clear cell renal cell carcinoma, and stress urinary incontinence.
Olaparib/abiraterone combination improves rPFS in mCRPC patients
AstraZeneca and Merck and Co., Inc., recently presented data that showed clinical improvement in median radiologic progression-free survival (rPFS) with olaparib (Lynparza) in combination with abiraterone (ZYTIGA) compared to abiraterone monotherapy in metastatic castration-resistant prostate cancer (mCRPC). Olaparib is being jointly developed and commercialized by AstraZeneca and Merck. The results of Study 08, a randomized, double-blinded, multicenter phase II trial, comparing olaparib in combination with abiraterone (n=71) to abiraterone monotherapy (n=71) in patients with previously treated mCRPC, regardless of homologous recombination repair mutation status, were presented at the American Society of Clinical Oncology annual meeting in Chicago and published in Lancet Oncology (2018; 19:975-86).The primary endpoint was rPFS. Secondary endpoints included time to second progression or death, overall survival, and health-related quality of life. Median rPFS was 13.8 months with olaparib and abiraterone compared to 8.2 months with abiraterone alone (HR: 0.65; 95% CI: 0.44-0.97; p=.034). Median time to second progression or death was 23.3 months versus 18.5 months (HR: 0.79; 95% CI: 0.51-1.21). Median overall survival was 22.7 months with combination treatment versus 20.9 months with abiraterone alone (HR: 0.91; 95% CI: 0.60-1.38).
Durable responses seen with metastatic urothelial cancer agent
Recently presented phase II data indicate that treatment with Janssen Pharmaceutical’s erdafitinib, a once-daily oral pan-fibroblast growth factor receptor (FGFR) inhibitor, resulted in durable responses in patients with metastatic or surgically unresectable urothelial cancer and FGFR alterations, a population with high unmet need based on poor outcomes when treated with available therapies. BLC2001 (NCT02365597) is a multicenter, open-label study evaluating the efficacy and safety of erdafitinib in the treatment of adult patients with locally advanced or metastatic urothelial cancer, whose tumors have certain FGFR alterations. Ninety-nine patients were treated with an optimized dosing schedule using pharmacodynamically guided dose up-titration: a starting dose of erdafitinib at 8 mg daily, with the possibility to increase the dose to 9 mg daily based on serum phosphate levels. There was a 40% confirmed overall response rate (RECIST 1.1; 3% complete response, 37% partial response), a median progression-free survival of 5.5 months, and median overall survival of 13.8 months, according to Janssen. The data were presented at the American Society of Clinical Oncology annual meeting in Chicago.
Genomic assay data presented for bladder, kidney cancers
New data generated from Foundation Medicine, Inc.’s comprehensive genomic profiling (CGP) assays were presented at the American Society of Clinical Oncology annual meeting in Chicago. One study outlined new data from PURE-01, a phase II study evaluating neoadjuvant pembrolizumab (Keytruda) in urothelial bladder cancer. The findings demonstrate the ability of CGP to detect genomic biomarkers (RB1, PBRM1, and tumor mutational burden) when combined with T-cell inflammation signatures to potentially predict response to immunotherapy, according to Foundation Medicine. In another study, CGP was performed on more than 140,000 solid tumors and hematologic malignancies and found that PBRM1 alterations were highly enriched in clear cell renal cell carcinoma (45%) compared with other tumor types (2.6%).
Next: Randomized study initiated for oxalate-reducing enzymeRandomized study initiated for oxalate-reducing enzyme
Captozyme, Inc. is initiating a prospective double-blind, randomized, placebo-controlled, crossover study with Nephure, an oxalate-reducing enzyme, to determine the extent to which Nephure versus placebo reduces urinary oxalate excretion (mg/24 hour) in healthy subjects who are provided a controlled diet. The key ingredient in Nephure was developed as a food ingredient to reduce both soluble and insoluble oxalate from a variety of foods and beverages. Nephure has the ability to degrade oxalate in food over a wide pH range, including the acidic pH of the stomach, according to Captozyme. About 80% of patients who develop kidney stones form calcium stones, mostly from calcium oxalate.
Phase II data: Clear cell RCC treatment combo well tolerated
X4 Pharmaceuticals announced positive clinical results from the phase II expansion of an ongoing phase I/II study of X4P-001-IO in combination with axitinib (Inlyta) in patients with clear cell renal cell carcinoma (ccRCC). The results were the first from the phase II portion of the study and demonstrated that the combination was well tolerated with a manageable safety profile and had encouraging response in heavily pretreated patients. In patients with ccRCC, the combination treatment of X4P-001-IO, a CXCR4 antagonist, and axitinib, a VEGFR kinase inhibitor, showed an objective response rate of 23%, including one patient with a confirmed complete response, X4 Pharmaceuticals reported. Nearly 75% of patients received at least two prior lines of therapy prior to entering the study. The data were presented at the American Society of Clinical Oncology annual meeting in Chicago.
Agreement will help launch prostate cancer biomarker test
MDxHealth SA has announced a worldwide licensing agreement with Koninklijke Philips N.V. for the rights to manufacture and market Philips' recently validated prognostic biomarker for prostate cancer, phosphodiesterase-4D7 (PDE4D7), as a prognostic test. The agreement enables MDxHealth to prepare the launch of its InformMDx test for prostate cancer, a tissue-based test utilizing PDE4D7 that can stratify patients according to their risk of disease progression and the development of secondary tumors. MDxHealth said it anticipates that InformMDx will provide actionable information to help clinicians guide post-biopsy treatment decisions at the time of diagnosis, as well as post-surgical treatment decisions following prostatectomy.
Next: Phase IV trial of testosterone nasal gel recruiting participantsPhase IV trial of testosterone nasal gel recruiting participants
A phase IV trial (NCT03203681) that will evaluate the impact of testosterone nasal gel (Natesto) use on sperm count is currently recruiting at the University of Miami department of urology. Researchers aim to enroll 40 men with confirmed hypogonadism (T <350 ng/dL on two samples). Each participant will take 11 grams of testosterone nasal gel three times per day for 24 weeks. FSH, LH, estradiol, testosterone, and semen analysis will be assessed after 12 and 24 weeks of treatment. The subjects will also be given Sexual Health Inventory for Men and quality of life questionnaires, which will be repeated after 25 weeks of treatment.
Positive 6-month data reported for SUI technology platform
Viveve reported positive and sustained 6-month data from an ongoing single-arm feasibility study using its cryogen-cooled, monopolar radiofrequency (CMRF) technology platform for the treatment of mild-to-moderate stress urinary incontinence (SUI) in women. This single-arm feasibility study included 36 subjects with mild to moderate SUI (based on the 1-hour pad weight test) who underwent treatment with Viveve’s CMRF technology under a proprietary treatment protocol. Currently, 29 subjects have successfully completed the 6-month follow-up. One-hour pad weight changed from 6.2 grams at baseline to 1.7 grams at 6 months, while daily incontinence episode frequency went from 2.0 at baseline to 1.0 at 6 months.