AMO959 with Lutetium‑177 PSMA‑617 plus ARPI for PSMA‑positive metastatic castration‑resistant prostate cancer
A Phase Ib/II Open-label, Multi-center Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With an Androgen Receptor Pathway Inhibitor (ARPI) in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC)
This trial tests whether adding the experimental drug AMO959 to lutetium‑177 PSMA therapy together with an androgen receptor pathway inhibitor can help adults with PSMA‑positive metastatic castration‑resistant prostate cancer who have already received one ARPI.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 123 (estimated) |
| Ages | 18 Years and up |
| Sex | Male |
| Sponsor | Novartis Industry-sponsored |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 12 sites (El Paso, Texas and 11 other locations) |
| Trial ID | NCT07226986 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates are adults with PSMA‑PET–positive metastatic castration‑resistant prostate cancer who progressed after one ARPI, have castrate testosterone levels, and have ECOG 0–2, with Phase II participants not having received taxane chemotherapy for mCRPC.
Not a fit: Patients with PSMA‑negative disease, non‑adenocarcinoma histology (for example neuroendocrine), inability to tolerate lutetium therapy or ARPI, or poor performance status are unlikely to benefit from this regimen.
Why it matters
Potential benefit: If successful, the combination could improve tumor control and delay progression in patients with PSMA‑positive mCRPC.
How similar studies have performed: Lutetium‑177 PSMA therapy has demonstrated survival benefit in prior late‑phase trials, but combining Lu‑PSMA with novel agents like AMO959 is investigational and has limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
El Paso, Texas and 11 other locations
- 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)
- Novartis Investigative Site — Murdoch, Western Australia, Australia (Recruiting)
- Novartis Investigative Site — Clermont-Ferrand, France (Recruiting)
- Novartis Investigative Site — Nantes, France (Recruiting)
- Novartis Investigative Site — Essen, Germany (Recruiting)
- Novartis Investigative Site — Sapporo, Hokkaido, Japan (Recruiting)
- Novartis Investigative Site — Granada, Andalusia, Spain (Recruiting)
- Novartis Investigative Site — Barcelona, Spain (Recruiting)
- Novartis Investigative Site — Madrid, Spain (Recruiting)
Study contacts
- Study coordinator: Novartis Pharmaceuticals
- Email: novartis.email@novartis.com
- Phone: 1-888-669-6682
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.