docetaxel oral/ritonavir (ModraDoc006/r) / Modra Pharma - LARVOL DELTA

Oral Docetaxel (ModraDoc/r) in Combination With Hormonal Treatment and Radiation Therapy in High-risk Prostate Cancer (clinicaltrials.gov) - P1 | N=24 | Terminated | Sponsor: The Netherlands Cancer Institute | Unknown status ➔ Terminated; low inclusion of patients and availability of the IP

Combination therapy • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=135 | Completed | Sponsor: Modra Pharmaceuticals | Phase classification: P2b ➔ P2 | N=102 ➔ 135

Enrollment change • Metastases • Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A global phase II randomized trial comparing oral taxane ModraDoc006/r to intravenous docetaxel in metastatic castration resistant prostate cancer. (PubMed, Eur J Cancer) - "ModraDoc006/r potentially represents a widely applicable, convenient, effective, and better tolerated oral taxane therapy option for mCRPC. Further investigation of ModraDoc006/r in a large randomized trial is warranted."

Journal • Metastases • P2 data • Alopecia • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Immunology • Metastatic Castration-Resistant Prostate Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

A Global Phase II Randomized trial comparing Oral Taxane ModraDoc006/r to Intravenous Docetaxel in Metastatic Castration Resistant Prostate Cancer (Eur J Cancer) - P2 | N=102 | NCT04028388 | Sponsor: Modra Pharmaceuticals | "There was no significant difference in rPFS between the 2 arms (p=0.1465). Median rPFS was 9.5 months and 11.1 months (95% CI) for ModraDoc006/r and i.v. docetaxel, respectively. Partial response was noted in 44.1% and 38.7% measurable disease patients, and 50% decline of PSA was seen in 23 (50%) and 26 (56.5%) evaluable cases treated with ModraDoc006/r and i.v. docetaxel, respectively. The safety profile of ModraDoc006/r 20-20/200-100 mg dose was significantly better than i.v. docetaxel, with mild (mostly Grade 1) gastrointestinal toxicities, no hematologic adverse events, and neuropathy and alopecia incidence of 11.5% and 25%, respectively."

P2 data • Metastatic Castration-Resistant Prostate Cancer

Impact of loperamide on the pharmacokinetics and tissue disposition of ritonavir-boosted oral docetaxel therapy; a preclinical assessment. (PubMed, Cancer Chemother Pharmacol) - "These results suggest that delayed loperamide administration can be added to ritonavir-boosted oral docetaxel treatment, without affecting the overall systemic exposure of docetaxel."

Journal • PK/PD data • Preclinical • CYP3A4

A phase 2 randomized study of oral docetaxel plus ritonavir (ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2022) - P2b | "Background: Intravenous (IV) docetaxel and oral prednisone is a standard of care regimen in patients (pts) with mCRPC...The ModraDoc006 and ritonavir combination is active in multiple docetaxel and cabazitaxel-resistant prostate cancer cell-lines The oral combination (ModraDoc006/r) was compared to IV docetaxel in a randomized phase 2b study in pts with mCRPC evaluating two doses of ModraDoc006/r (30-20/200-100 mg and 20-20/200-100 mg)...Prior therapy with enzalutamide in 8 pts, abiraterone in 10 pts... ModraDoc006/r demonstrated a favorable safety profile and comparable efficacy to IV docetaxel in pts with mCRPC, thus providing a compelling rationale for conduct of an expanded pivotal program. A key clinical program focus is the comparison of ModraDoc006/r to best available therapy in refractory mCRPC. Studies of ModraDoc006/r in other malignancies are also in active development."

Clinical • P2 data • Alopecia • Anemia • Dental Disorders • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Prostate Cancer • Solid Tumor • Stomatitis

"Modra Pharmaceuticals Announces U.S. Patent Issuance for ModraDoc006/r https://t.co/07CCqDKlx8" (@NewsFromBW)

Modra Pharmaceuticals Announces U.S. Patent Issuance for ModraDoc006/r (Businesswire) - "Modra Pharmaceuticals ('Modra') today announced that the U.S. Patent and Trademark Office (USPTO) has issued to Modra U.S. Patent No. 11,571,408, covering the use of its oral taxane therapeutic ModraDoc006/r....The patent provides protection for ModraDoc006/r until 2039....The patent covers the use of Modra’s compound, ModraDoc006, an oral formulation of docetaxel, at doses which control side effects by preventing elevated peak plasma levels of docetaxel, while maintaining an effective plasma level of docetaxel to eradicate tumor cells...Modra is planning for a Phase 3 pivotal trial in mCRPC patients."

New P3 trial • Patent • Genito-urinary Cancer • Oncology • Prostate Cancer

[VIRTUAL] Phase IIb trial of oral ModraDoc006/r as a tolerable and effective option in comparison with intravenous docetaxel in metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2021) - P2b | "Adverse events of cytopenias and alopecia were lower with ModraDoc006/r, and preliminary efficacy appears comparable in both arms. Oral chemotherapy option has become critically important during the COVID-19 pandemic. Preliminary data reveals that ModraDoc006/r is an attractive oral option in mCRPC with favorable toxicity profile and comparable efficacy."

P2b data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A multicenter phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic castration-resistant prostate cancer (mCRPC), suitable for treatment with a taxane (NCT04028388). (ASCO-GU 2020) - P2b; "ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388. Research Funding: Modra Pharmaceuticals."

Clinical • P2b data

ModraDoc006, an oral docetaxel formulation in combination with ritonavir (ModraDoc006/r), in metastasized castration-resistant prostate cancer (mCRPC): A multicenter phase I study. (ASCO-GU 2020) - P1; " Progressive mCRPC patients, who were treatment naïve or previously treated with either abiraterone or enzalutamide, received a maximum of 30 weekly cycles of ModraDoc006/r in a bi-daily once weekly (BIDW) schedule. The RP2D of BIDW ModraDoc006/r in mCRPC was established as 30-20/200-100 mg. These results are encouraging for further development of ModraDoc006/r as a convenient, safe and effective alternative to IV docetaxel for mCRPC patients. A phase 2b study is currently being conducted."

Clinical • Combination therapy • P1 data • KLK3

Time above threshold plasma concentrations as pharmacokinetic parameter in the comparison of oral and intravenous docetaxel treatment of breast cancer tumors. (PubMed, Anticancer Drugs) - "ModraDoc006/r is superior to i.v. docetaxel 75 mg/m2 in terms of median time above cytotoxic threshold levels <0.078 µmol/L. This may indicate superior cytotoxicity and inhibition of tumor growth compared to i.v. administration for relatively docetaxel-sensitive tumors."

Journal • PK/PD data • Breast Cancer • Oncology • Solid Tumor

Phase 2 randomized trial of ModraDoc006/r, oral docetaxel plus ritonavir, versus intravenous docetaxel in metastatic castration resistant prostate cancer (mCRPC). (ASCO-GU 2022) - P2b | "Hematological toxicities and adverse events neuropathy and alopecia were lower with ModraDoc006/r than with IV docetaxel. ModraDoc006/r represents a convenient, oral, tolerable option for patients with mCRPC. ModraDoc006/r has comparable efficacy and a favorable tolerability profile as compared to IV docetaxel and merits further development in patients with mCRPC."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Ulka N. Vaishampayan, MBBS, Examines Oral Formulation of Docetaxel With Ritonavir, ModraDoc006/r, in Metastatic CRPC (Cancer Network) - "Ulka N. Vaishampayan, MBBS, discussed the potential benefits of oral docetaxel plus ritonavir in metastatic castration-resistant prostate cancer....We hope ModraDoc006/r will allow the majority of patients with mCRPC to benefit [from docetaxel]."

Media quote

ModraDoc006 Plus Ritonavir Shows Favorable Safety, Comparable Efficacy to IV Docetaxel in mCRPC (OncLive) - "The combination of ModraDoc006-a novel, oral tablet formulation of docetaxel-and ritonavir produced comparable response rates and radiographic progression-free survival to that achieved with intravenous docetaxel in patients with metastatic castration-resistant prostate cancer....'The study results make a compelling rationale for evaluating this convenient, oral, effective, and well-tolerated therapy in an expanded pivotal program,' lead study author Ulka Nitin Vaishampayan, MBBS."

Media quote

Modra Pharmaceuticals Presents In-Depth Data Analysis from Lower Dose Cohort in Phase 2b Study of Oral Taxane ModraDoc006/r in mCRPC Patients at 2022 ASCO Annual Meeting (Businesswire) - "'Not only did ModraDoc006/r 20-20 eliminate neutropenia, a significant hurdle in the oral taxane space, while maintaining equivalent efficacy to IV docetaxel, it also dramatically reduced neuropathy and alopecia, side-effects that frequently complicate the lives of mCRPC patients undergoing chemotherapy,' said Ulka Vaishampayan, MD...'These encouraging data provide a compelling rationale for conducting further development in a pivotal study with ModraDoc006/r to further investigate its potential. ModraDoc006/r 20-20 will be applicable to a broader mCRPC patient population that may not have access to or tolerate more traditional IV chemotherapy regimens. The convenience of oral administration with maintained efficacy makes it an attractive option that is likely to improve prostate cancer outcomes."

Media quote

Modra Pharmaceuticals to Present New Phase 2b Data at the 2022 ASCO General Annual Meeting on ModraDoc006/r, a Boosted Oral Taxane for Patients with Metastatic Prostate Cancer (Businesswire) - "Modra Pharmaceuticals...announced that the company will present new data from its Phase 2b trial evaluating ModraDoc006/r, a boosted oral taxane therapeutic versus the standard-of-care IV chemotherapy docetaxel, in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) at the upcoming ASCO General Annual Meeting held from June 3 - 7, 2022 virtually and in-person in Chicago, IL, USA."

P2b data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

Modra Pharmaceuticals Presents Positive Phase IIb Results for ModraDoc006/r, a Boosted Oral Taxane for Patients with Metastatic Prostate Cancer, at 2022 ASCO GU Annual Meeting (Businesswire) - P2 | N=102 | NCT04028388 | Sponsor: Modra Pharmaceuticals | "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 Genitourinary Cancers Symposium (ASCO GU) held from February 17-19, 2022....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."

P2b data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer (clinicaltrials.gov) - P2b | N=102 | Completed | Sponsor: Modra Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ModraDoc006/r in Patients With Breast Cancer (clinicaltrials.gov) - P2a; N=12; Completed; Sponsor: Modra Pharmaceuticals; Recruiting ➔ Completed; N=24 ➔ 12; Trial completion date: Jan 2020 ➔ Nov 2020

Clinical • Enrollment change • Trial completion • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2 • MRI

ModraDoc006/r in Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1; N=23; Completed; Sponsor: Modra Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Extended Use of ModraDoc006/r (clinicaltrials.gov) - P1; N=17; Completed; Sponsor: Modra Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Oncology • Solid Tumor

Food Effect Study of ModraDoc006 in Combination With Ritonavir (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: Modra Pharmaceuticals; Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • ABCB1 • ABCC2

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer (clinicaltrials.gov) - P2b; N=102; Active, not recruiting; Sponsor: Modra Pharmaceuticals; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2021 ➔ Nov 2021; Trial primary completion date: Dec 2020 ➔ Aug 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Addition of an oral docetaxel treatment (ModraDoc006/r) to androgen deprivation therapy (ADT) and intensity-modulated radiation therapy (IMRT) in patients with high risk N+M0 prostate cancer (ESMO 2019) - P1; "Legal entity responsible for the study: Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL). Funding: Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL)."

Clinical