In the phase 1b/2 study, VERU-111 was associated with reductions in prostate-specific antigen (PSA), objective tumor responses and durable activity in men with previously treated mCRPC, Dr. Mark Markowski of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, reported at the virtual 2020 meeting of the European Society for Medical Oncology (ESMO).
The phase 1b portion of the study enrolled 39 men (median age, 74) with mCRPC at seven centers in the United States; both abiraterone and enzalutamide had failed in 44% of these men; 55% had bone-only metastatic disease and nine (23%) had previously received taxane.
This safety and dose-finding study used a two-part dose escalation strategy followed by an expanded dose and dose schedule of VERU-111 daily continuous dosing until disease progression or toxicity.
The maximum tolerated dose was 72 mg per day. No grade-3 diarrhea was observed at doses less than 72 mg per day. At below 72 mg/d, the most common side effects were mild to moderate nausea, vomiting, diarrhea and fatigue, with no observed neurotoxicity or neutropenia.
Twenty-five patients in the phase 1b study have been dosed with 63 mg/d for at least one cycle and 10 have reached at least four 21-day cycles of continuous dosing. Six of these patients saw their PSA decline. Four had at least a 30% decline and two had at least a 50% PSA decline.
Based on standard criteria, objective tumor responses were seen in two of 10 patients. Seven patients had stable disease. Five of the 10 patients are continuing on treatment.
The median time to radiographic progression was more than 11 months. "Based upon the literature, the median radiographic-progression-free survival for men on an alternative androgen-receptor-targeting agent, abiraterone or enzalutamide, is approximately 3.4 months," Dr. Mitchell Steiner, study investigator and CEO of Veru Inc, which is developing the drug and funded the study, told Reuters Health by email.
"VERU-111's median duration of treatment without prostate cancer progression in the Phase 1b clinical trial is greater than 11 months with some men now on treatment for more than 17 months," he noted.
Dr. Steiner said VERU-111 is unique from a number of perspectives including its route of administration (oral) and its mechanism of action.
"All current chemotherapeutic agents used for the treatment of metastatic prostate cancer are given intravenously (IV). This is important in that the dosing and schedule are different as these IV drugs are only given once every 3 weeks whereas VERU-111 can be given daily providing for continuous dosing," he explained.
"Mechanistically, VERU-111 is distinct from current clinical agents used for the treatment of prostate cancer. VERU-111 is a cytoskeletal disruptor that, in addition to its inhibition of microtubule assembly, impacts other elements of the cytoskeleton including the intermediate filaments. VERU-111 is not pumped out of cancer cells by p-glycoprotein or other multi-drug-resistance proteins, which is a common resistance mechanism used by cancer cells," he said.
"Finally, VERU-111 is able to address one of the most rapidly growing unmet medical needs in men with metastatic castration-resistant prostate cancer who have also failed one of the androgen-receptor-targeting agents. The only current option is the off-label use of IV taxane chemotherapy," Dr. Steiner said.
The phase-2 portion of the current trial is ongoing and the company anticipates starting a phase-3 trial during the first quarter of 2021.
By Megan Brooks
SOURCE: https://bit.ly/3iRRnou European Society for Medical Oncology (ESMO) 2020 Congress, presented September 18, 2020.
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