AMO959 with Lutetium‑177 PSMA‑617 plus ARPI for PSMA‑positive metastatic castration‑resistant prostate cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

The study begins with a Phase Ib dose‑escalation portion using small cohorts (3–6 participants per dose level) to determine the recommended dose for expansion of AMO959 given first alone and then in combination with standard‑dose AAA617 (177Lu‑PSMA‑617) and an ARPI (abiraterone or enzalutamide). After the recommended dose(s) are identified, Phase II randomizes approximately 75 participants (about 25 per arm in a 1:1:1 ratio) to compare AMO959 plus AAA617 plus ARPI versus AAA617 plus ARPI regimens. Key eligibility requires PSMA‑PET positive mCRPC, prior exposure to one ARPI, castrate testosterone levels, and ECOG performance status 0–2, with Phase II excluding prior taxane use in the mCRPC setting. The trial will monitor safety, tolerability, pharmacokinetics, dose‑limiting toxicities in Phase Ib, and preliminary anti‑tumor activity in Phase II.

Why it matters

Who can join: the full rules

Key Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histologically confirmed adenocarcinoma of the prostate. Participants with other histology (e.g. neuroendocrine, intraductal subtype) are not eligible.
* Phase Ib: Prior exposure of up to 1 line of taxane-based chemotherapy is permissible. Phase II: Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease assessed by using a PSMA imaging agent that is approved as per protocol and are eligible as determined by the sponsor's central reading rules.
* Castration level of testosterone (\< 50 ng/dL), and/or use of concomitant ADT
* Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI), based on at least 1 of the following criteria:

  * Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines.
  * Soft-tissue progression defined PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016).
  * Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria Scher et al 2016).

Key Exclusion Criteria:

* Concurrent local (radiation therapy to the prostate with curative intent or other prostate antineoplastic ablative procedures) or systemic (hormonal ablation, chemotherapy, immunotherapy, , RLTs) antineoplastic treatments, or within 28 days of enrollment (Phase Ib) or randomization (Phase II)
* Prior treatment with any RLT or PSMA-targeted agents (approved or investigational)
* Any other investigational agents within 28 days prior to first dose of any study treatment
* Concurrent serious medical conditions that may interfere with study procedures or followup
* Participants with a history of CNS metastases must have received therapy (surgery, whole brain radiation therapy, stereotactic radiosurgery) and be neurologically stable, asymptomatic, and not taking corticosteroids for the purpose of maintaining neurologic integrity.

Other protocol-defined inclusion/exclusion criteria may apply.

Where it's running

• VA Greater LA Healthcare System
  Los Angeles, California, United States Recruiting
• Duke Univ Medical Center
  Durham, North Carolina, United States Recruiting
• Rio Grande Urology
  El Paso, Texas, United States Recruiting
• Utah Intermountain Medical Center
  Murray, Utah, United States Recruiting
• Novartis Investigative Site
  Malvern, Victoria, Australia Recruiting
• Novartis Investigative Site
  Melbourne, Victoria, Australia Recruiting

Study contacts

• Study coordinator: Novartis Pharmaceuticals
• Email: novartis.email@novartis.com
• Phone: 1-888-669-6682

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.