On February 17, 2022 Modra Pharmaceuticals ("Modra") reported positive data from its Phase IIb trial evaluating its boosted oral taxane therapeutic, ModraDoc006/r, in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) compared to the standard-of-care, the IV chemotherapy docetaxel (Press release, Modra Pharmaceuticals, FEB 17, 2022, View Source [SID1234608211]).
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ModraDoc006/r is an oral tablet formulation of docetaxel co-administered with ritonavir, a boosting agent which enhances bioavailability. In a total of 101 patients enrolled, ModraDoc006/r demonstrated a similar efficacy and an improved tolerability profile compared to IV docetaxel, with reduced neutropenia, neuropathy and alopecia. The trial data will be presented at the 2022 Annual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) held from February 17-19, 2022, one year after Modra shared its initial study data at the same conference.
"Completing this study is an exciting step for Modra, as we continue to demonstrate the potential of ModraDoc006/r to be a valuable alternative to IV chemotherapeutics for mCRPC," said Colin Freund, CEO of Modra Pharmaceuticals. "Our goal with ModraDoc006/r is to offer a better tolerated, effective and more convenient oral taxane therapeutic to patients with prostate cancer, including those who cannot tolerate or otherwise access IV therapy. Based on the currently reported compelling data, we are planning out the next development steps for ModraDoc006/r, including a pivotal study. We would like to extend our sincere thanks to the patients and clinicians who participated in this study."
Out of the total study population, 49 patients received IV docetaxel and 52 ModraDoc006/r (21 on 30-20/200-100 mg ("30-20") and 31 on 20-20/200-100 mg ("20-20") bi-daily weekly dosing (BIDW) doses). ModraDoc006/r vs IV docetaxel demonstrated an overall response rate (ORR) of 44% vs. 39%, respectively. Prostate- Specific Antigen (PSA) responses were comparable at 50% vs. 57%, respectively. Neutropenia (low levels of neutrophils, a type of white blood cell) was eliminated with ModraDoc006/r at the 20-20 mg dose, reduced to 14% at the 30-20 mg dose vs 25% on IV docetaxel. Neuropathy (nerve damage or dysfunction) and alopecia were also reduced with ModraDoc006/r at the 20-20 mg dose compared to the 30-20 mg dose and IV docetaxel. Gastrointestinal toxicities were slightly more frequent, but still predominantly mild, in the ModraDoc006/r arm at both dose levels.
"ModraDoc006/r has shown a favorable toxicity profile and comparable efficacy to IV docetaxel in metastatic CRPC. Advanced prostate cancer patients frequently do not receive the benefits of IV docetaxel chemotherapy due to advanced age, comorbidities and, during the pandemic, fear of exposure to Covid-19 at infusion centers. An oral chemo that is easier to tolerate – with less risk of cytopenias, hair loss and neuropathy – would make the benefits of chemo accessible to the majority of patients with metastatic prostate cancer. Thus, there is a compelling rationale to evaluate ModraDoc006/r further," said Ulka Vaishampayan, MD, Principal Investigator of the study and Professor of Internal Medicine, Division of Hematology/Oncology at the University of Michigan.
The open label 1:1 randomized study evaluated a ModraDoc006/r BIDW regimen versus IV docetaxel 75 mg/m2 in 21-day cycles. Initially a BIDW 30-20/200-100 mg dose (representing 30 mg ModraDoc006 and 200 mg ritonavir in the morning, 20 mg ModraDoc006 and 100 mg ritonavir in the evening) was administered on days 1, 8 and 15 of a 21-day cycle. After 21 patients, the morning dose of ModraDoc006 was reduced to 20 mg to improve tolerability. All patients received 5 mg oral prednisone twice daily. The primary endpoint of the study was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives were ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety assessments. Patient reported outcomes and health-related Quality of Life (QoL) was assessed with treatment satisfaction and Functional Assessment of Cancer Therapy-Prostate (FACTP) questionnaires at baseline and after cycles 3, 6 and 10.
About metastatic Castration-Resistant Prostate Cancer (mCRPC)
mCRPC is an advanced form of prostate cancer and the fourth most common cause of cancer death overall. mCRPC is not amenable to surgical treatment and resistant to androgen deprivation therapy, a hormone therapy used as initial disease management to reduce growth of prostate cancer cells.
About ModraDoc006/r
ModraDoc006/r is a proprietary boosted taxane therapy based on docetaxel, an intravenously administered therapy, that is very broadly used in a variety of tumor types. ModraDoc006 – an oral docetaxel tablet – is given in combination with ritonavir (r), which acts as a booster to increase the systemic bioavailability of ModraDoc006. ModraDoc006/r is designed to combine the convenience and practicality of taking chemotherapy treatment at home with the potential for an improved safety profile, as compared to standard IV docetaxel.