DS9051b for advanced or metastatic adrenocortical carcinoma and metastatic castration‑resistant prostate cancer

A Phase 1, First-in-human (FIH), Multicenter, Open-label Trial of DS9051b in Participants With Advanced or Metastatic Adrenocortical Carcinoma (ACC) and Metastatic Castration-resistant Prostate Cancer (mCRPC)

This trial will try an experimental drug called DS9051b in adults with advanced adrenocortical carcinoma or metastatic castration‑resistant prostate cancer to see if it is safe and shows early signs of benefit.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Daiichi Sankyo (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 6 sites (Sarasota, Florida and 5 other locations)
• Trial ID: NCT07189403 on ClinicalTrials.gov

What this trial studies

This is a phase 1, first‑in‑human dose‑escalation trial of DS9051b enrolling adults with histologically confirmed advanced or metastatic adrenocortical carcinoma (ACC) or metastatic castration‑resistant prostate cancer (mCRPC). The dose escalation portion seeks to define the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) while characterizing safety, tolerability, and pharmacokinetics. Investigators will monitor preliminary efficacy signals with tumor response assessments and relevant biomarkers. Participants must meet performance status and organ function criteria and, for mCRPC, have prior AR pathway inhibitor exposure.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed ACC or prostate adenocarcinoma with metastatic castration‑resistant disease, ECOG 0–1 (or ECOG 2 related to cancer pain), adequate organ and marrow function, and for mCRPC at least one prior ARPI therapy.

Not a fit: Patients without these specific cancers, those with poor organ function or performance status, uncontrolled medical problems, or who cannot attend frequent on‑site visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If DS9051b is safe and shows activity, it could provide a new treatment option that slows tumor growth or extends survival for people with these hard‑to‑treat cancers.

How similar studies have performed: This is a first‑in‑human trial of DS9051b; while other early‑phase targeted agents in mCRPC or ACC have occasionally shown promising signals, overall success has been limited and the approach remains experimental.

Eligibility criteria

General Inclusion Criteria for All Participants

1. Sign and date the main ICF, prior to the start of any trial-specific procedures.
2. Adults ≥18 years of age at the time the ICF is signed (Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old)
3. Histologically confirmed diagnosis of ACC or adenocarcinoma of the prostate
4. ECOG PS of 0 or 1 assessed no more than 14 days prior to C1D1. (ECOG PS of 2 due to cancer pain is acceptable)
5. Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to C1D1 as defined below. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days of initiation of trial intervention as appropriate.

   Additional Inclusion Criteria for Participants with mCRPC
6. Treatment with at least 1 line (or more) of ARPI therapy for CSPC or in CRPC for a minimum of 12 weeks (eg, abiraterone, enzalutamide, darolutamide, apalutamide).
7. Treatment with at least 1 line (or more) of chemotherapy, having ineligibility for chemotherapy or refusal of chemotherapy.
8. Documented disease progression by one or more of the following criteria:

   * PSA progression as defined by PCWG3 criteria.
   * Soft tissue disease progression as defined by RECIST 1.1 criteria.
   * Bone disease progression as defined by Prostate Cancer Working Group 3 criteria.

An individual who meets any of the following criteria will be excluded from participation in this trial:

1. History of pituitary gland dysfunction.
2. Active or uncontrolled autoimmune disease requiring systemic treatment.
3. Any medical condition (other than the cancer disease) requiring a dose of concurrent systemic corticosteroid treatment greater than 5 mg of prednisone and/or 100 μg of fludrocortisone per day (or equivalent).
4. Active infection or other medical conditions that would make corticosteroids contraindicated.
5. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated, clinically progressive, symptomatic, or requiring systemic therapy with corticosteroids or anticonvulsants or local therapy (ie, radiotherapy) to control associated symptoms.
6. Uncontrolled or significant cardiovascular disease.
7. History of another primary malignancy (beyond the indication\[s\] under study) except for:

   * Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of trial intervention and of low potential risk for recurrence.
   * Non-melanoma skin cancer, lentigo maligna, or lentigo maligna melanoma treated with curative intent and without evidence of disease.
   * Carcinoma in situ treated with curative intent and without evidence of disease.
   * Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who, in the opinion of the investigator, are not deemed to require active intervention.
8. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, Grade ≤1 or baseline.
9. Participants who cannot swallow whole DS9051b tablets and/or follow DS9051b administration schedule at protocol-defined frequency due to some reasons (eg, dysphagia etc).
10. Known gastrointestinal disease or gastrointestinal procedure that may interfere with absorption of trial intervention including proton pump inhibitors and antacids.

Where this trial is running

Sarasota, Florida and 5 other locations

• Florida Cancer Specialists — Sarasota, Florida, United States (Recruiting)
• Columbia University — New York, New York, United States (Not_yet_recruiting)
• Brown University — Providence, Rhode Island, United States (Recruiting)
• Oncopole Claudius Regaud — Toulouse, France (Recruiting)
• Centre Oscar Lambret — Villejuif, France (Not_yet_recruiting)
• Royal Marsden — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Daiichi Sankyo Contact for Clinical Trial Information

Conditions Advanced or Metastatic Adrenocortical Carcinoma; Metastatic Castration-resistant Prostate Cancer; Advanced or metastatic adrenocortical carcinoma; Metastatic castration-resistant prostate cancer