opevesostat (MK-5684) / Orion Corp, Merck (MSD) - LARVOL DELTA

IDeate-Prostate02: A PHASE 1/2, OPEN-LABEL UMBRELLA SUBSTUDY OF IFINATAMAB DERUXTECAN-BASED TREATMENT COMBINATIONS OR AS MONOTHERAPY IN PARTICIPANTS WITH PREVIOUSLY TREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (SUO 2025) - P1/2 | "Two monotherapy arms (Arm 1 [docetaxel] and Arm 2 [I-DXd]) will enroll participants into the Efficacy Phase, and 2 I-DXd combination arms (Arm 3: I-DXd+MK-5684; and Arm 4: I-DXd+ARPI [abiraterone acetate or enzalutamide; prior treatment dependent]) will enroll into the Safety Lead-in, followed by Efficacy Phase. Recruitment is ongoing. "

Clinical • Metastases • Monotherapy • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov) - P3 | N=1314 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CYP11A1 INHIBITOR OPEVESOSTAT ALONE OR IN COMBINATION WITH OTHER THERAPIES FOR PARTICIPANTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: THE PHASE 1/2 OMAHA-01A SUBSTUDY (SUO 2025) - P1/2 | "In the efficacy phase, participants will be randomized 1:1:1:1 to receive opevesostat alone (5 mg PO BID; N≤100), or in combination with olaparib, docetaxel or cabazitaxel at the RP2D (~40 participants each). Secondary end points include ORR, DOR and radiographic PFS per PCWG-modified RECIST v1.1, and OS. "

Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A) (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Mar 2028 ➔ Jan 2029 | Trial primary completion date: Mar 2028 ➔ Jan 2029

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Evaluate the Effect of MK-5684 in Male Participants With Severe Renal Impairment (RI) and With End-stage Renal Disease (ESRD) (MK-5684-010) (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Nephrology • Renal Disease

OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov) - P3 | N=1314 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Dec 2030 ➔ May 2028

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Evaluate the Effect of MK-5684 in Male Participants With Severe Renal Impairment (RI) and With End-stage Renal Disease (ESRD) (MK-5684-010) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Kidney Disease • Nephrology • Renal Disease

CYP11A1 inhibitor opevesostat (MK-5684) alone or in combination with other therapies for participants (pts) with metastatic castration-resistant prostate cancer (mCRPC): the phase 1/2 OMAHA-U01 substudy 01A (DGU 2025) - P1/2 | "In the efficacy phase, pts will be randomly assigned 1:1:1:1 to receive opevesostat (5 mg PO BID), opevesostat 5 mg PO BID + olaparib (RP2D), opevesostat 5 mg PO BID + docetaxel (RP2D), and opevesostat 5 mg PO BID + cabazitaxel (RP2D). The primary end point for the safety phase is safety/tolerability. Primary end points for the efficacy phase are safety and PSA response rate per Prostate Cancer Working Group criteria (reduction from baseline in PSA of ≥50% at consecutive assessments ≥3 wk apart)."

Clinical • Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

OMAHA1: Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003) (clinicaltrials.gov) - P3 | N=1310 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005) (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2026 ➔ Apr 2026 | Trial primary completion date: Jan 2026 ➔ Apr 2026

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov) - P3 | N=1500 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015) (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2030 ➔ Nov 2027 | Trial primary completion date: Jul 2030 ➔ Nov 2027

Enrollment open • Pan tumor • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

OMAHA-004: Phase 3 trial of CYP11A1 inhibitor opevesostat versus next-generation hormonal agent (NHA) switch in participants with metastatic castration-resistant prostate cancer after 1 prior NHA (UAA 2025) - No abstract available

Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

OMAHA-003: Phase 3 trial of CYP11A1 inhibitor opevesostat versus next-generation hormonal agent (NHA) switch in participants with metastatic castration-resistant prostate cancer after NHA and taxane-based chemotherapy (UAA 2025) - No abstract available

Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CYPIDES: Safety and Pharmacokinetics of ODM-208 in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=204 | Active, not recruiting | Sponsor: Orion Corporation, Orion Pharma | Trial completion date: Jun 2025 ➔ Jul 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

OMAHA1: Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003) (clinicaltrials.gov) - P3 | N=1200 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Clinical Study of Ifinatamab Deruxtecan Based Treatment Combinations or as Monotherapy to Treat Metastatic Castrate Resistant Prostate Cancer (mCRPC) (MK-2400-01A/IDeate-Prostate02) (clinicaltrials.gov) - P1/2 | N=360 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Drug-Drug Interaction Study of Carbamazepine and Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-012) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion

A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015) (clinicaltrials.gov) - P2 | N=250 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Pan tumor • Oncology • Solid Tumor

Orion’s collaborator, MSD, expands clinical development program for opevesostat to women’s cancers (GlobeNewswire) - "Orion’s collaborator, MSD, has expanded the development program for opevestostat (MK-5684) to now include women’s cancers. A new Phase 2 clinical trial evaluating the safety and efficacy of opevesostat for the treatment of breast, endometrial and ovarian cancers has been posted to ClinicalTrials.gov database."

Trial status • Endometrial Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Ovarian Cancer • Solid Tumor

Discovery of ACE-232: a novel and highly potent non-steroidal CYP11A1 inhibitor (AACR 2025) - "In castrated mouse models, ACE-232 showed equal or superior efficacy in inhibiting tumor growth at 0.3 mg/kg QD in both VCaP and enzalutamide-resistant xLNCaP models, compared to ODM-208 at 30 mg/kg BID. GLP toxicology studies demonstrated a wide safety margin in both rats and dogs, with primary effects observed in the endocrine and reproductive organs, consistent with CYP11A1 inhibition. Based on these findings, an IND filing for ACE-232 with the FDA is planned for December 2024."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

HSK46575: A best-in-class, long lasting, small molecular CYP11A1 inhibitor for the treatment of castration-resistant prostate cancer (CRPC) (AACR 2025) - "Approximately half of the castration-resistant prostate cancer (CRPC) patients will benefit from abiraterone or enzalutamide treatment initially...Notably, 2.5 mg/kg/day dosage of HSK46575 exhibited superior efficacy compared to Abiraterone (200 mg/kg/day) and ODM-208 (60 mg/kg/day)... HSK46575 potently blocks the CYP11A1 enzymatic activity and the biosynthesis of Preg and TE at low nM concentrations in vitro. In normal male rats, the inhibition of both Preg and TE by HSK46575 was dose-dependent and long-lasting. In the LNCap (with AR-T877A) castrated xenograft model, HSK46575 significantly inhibited tumor growth and serum PSA level at a low dosage of 1 mg/kg/day."

Late-breaking abstract • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Evaluate Opevesostat (MK-5684) in Male Participants With Moderate Hepatic Impairment (MK-5684-009) (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

Pharmacokinetics (PK) of the novel nonsteroidal CYP11A1 inhibitor opevesostat (ODM-208/MK-5684): Interaction potential with midazolam and effect of food (AACR 2025) - "Opevesostat and its metabolite M1 did not inhibit CYP3A4-mediated metabolism and can be safely co-administered with other drugs metabolized through this pathway. Total exposure for opevesostat was not impacted by food. A decrease in opevesostat Cmax and delay in Tmax with a high-fat meal was not unexpected; this observation is unlikely to impact clinical practices around opevesostat administration."

PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CYP3A4

Steroid metabolism mediates renal cancer bone-specific metastasis (AUA 2025) - "In vivo, treatment with Opevesostat (30mg/kg, daily), an oral selective high-potency CYP11A1 inhibitor, effectively reduced the tumor burden of bone metastasis in OBM model mice and prolonged their survival time. These findings suggest a new role of steroid metabolism in modulating RCC bone metastases formation. Blocking steroid metabolism could be a promising therapeutic target for this malignant disease."

Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor