ASCO GU 2021: Phase IIb Trial of Oral ModraDoc006/ritonavir as a Tolerable and Effective Option in Comparison with Intravenous Docetaxel in mCRPC

( ModraDoc006 is a novel, oral tablet formulation of docetaxel. To enhance bioavailability, it is co-administered with ritonavir (r), an inhibitor of cytochrome P450 3A4 and P-glycoprotein. The oral combination, noted as ModraDoc006/r, has potential advantages in terms of patient convenience, elimination of infusion-related reactions, and avoiding prophylactic steroid administration, as well as safety benefits. At the GU ASCO 2021 annual meeting, Dr. Ulka Vaishampayan and colleagues presented efficacy results of the Phase IIb trial comparing oral ModraDoc006/r to IV docetaxel.

This trial is an open-label 1:1 randomized phase IIb trial of ModraDoc006/r bi-daily once weekly (BIDW) regimen versus IV docetaxel 75 mg/m2 q day 21. Initially, BIDW 30-20 mg ModraDoc006 combined with 200-100 mg ritonavir was administered on days 1, 8, and 15 of a 21-day cycle. After 39 patients, the dose of ModraDoc006 was reduced to 20-20 mg BIDW to improve GI tolerability. All patients received 5 mg oral prednisone BID. Imaging was obtained every 8-9 weeks for the first 24 weeks, and every 12 weeks thereafter. Initially, mCRPC patients with RECIST 1.1 measurable disease were eligible, but this was amended to evaluable disease per Prostate Cancer Working Group 3 (PCWG3) to allow for wider recruitment. No prior taxane therapy was allowed. The primary efficacy endpoint was radiographic progression free survival per PCWG3 criteria, and secondary endpoints included objective response rate, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety. Patient-reported outcomes, QoL, and FACT-P questionnaires were also assessed. A sample size of approximately 50 evaluable patients per arm will provide a point estimate of the primary endpoint of rPFS for this study. The trial design is as follows:


At the time of preliminary analysis, 98 patients were enrolled in the US and European Union, 49 patients in each arm, with 55 patients currently on treatment:


Preliminary activity data show that ModraDoc006/r has an impact on PSA levels, comparable to that of IV docetaxel:


At the time of analysis radiographic progression free survival data was immature. ModraDoc006/r was mainly associated with mild and reversible GI-toxicity, of which grade and incidence were reduced at 20-20 mg compared to the initial dose-level of 30-20 mg ModraDoc006. Myelosuppression and neurotoxicity were low to negligible in the ModraDoc006/r arm, with low accompanying levels of alopecia.

Dr. Vaishampayan concluded this presentation of the early efficacy data for ModraDoc006/r with the following take-home messages:

  • Adverse events of cytopenias and alopecia were lower with ModraDoc006/r, with the additional benefit of eliminating the infusion reactions
  • Preliminary efficacy was noted, with >50% of all patients ongoing treatment and encouraging signs of response for ModraDoc006/r
  • An oral chemotherapy option has become critically important during the COVID-19 pandemic, and preliminary data reveals that ModraDoc006/r is an attractive oral option in mCRPC with favorable toxicity profile and comparable efficacy to traditional IV treatment
Presented by: Ulka N. Vaishampayan, MD, Michigan Medicine Urology Oncology Clinic

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2020