Last Update: Aug 18, 2026 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) ClinicalTrials.gov Identifier: [NCT07226986](https://clinicaltrials.gov/ct2/show/NCT07226986) Novartis Reference Number:CAMO959A12103 [See if you Pre-qualify](#trial-eligibility "See if you Pre-qualify") All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. ## Study Description The purpose of this phase Ib/II study is to (a) in Phase Ib evaluate the safety, tolerability, and pharmacokinetics (PK) of AMO959 when given in combination with lutetium (177Lu) vipivotide tetraxetan (also known as \\\[177Lu\\\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter referred to as AAA617) with an androgen receptor pathway inhibitor (ARPI) in participants with metastatic castration resistant prostate cancer (mCRPC) who have failed one prior ARPI and with or without prior taxane exposure, and (b) in Phase II evaluate the preliminary efficacy of AMO959 in combination with AAA617 and ARPI in participants with mCRPC who have failed one prior ARPI, but who have not yet been exposed to taxane treatment. This study will consist of two phases: 1\. The escalation phase (Ib) will consist of provisionally three dose level cohorts of 3-6 participants investigating the safety, tolerability, and to determine the recommended dose for expansion (RDE) of AMO959 with standard dose of AAA617 +/- ARPI (abiraterone or enzalutamide). Initially AMO959 monotherapy will be administered, and then AMO959 will be given along with AAA617 in the same participants. Dose escalation meetings (DEMs) will occur when all participants in a dose level cohort have completed the DLT evaluation period or have experienced a DLT prior to the end of the evaluation period. 2\. The Phase II will follow with 25 participants per arm randomized in a 1:1:1 ratio treated at the RDE(s) of AMO959 along with AAA617 and ARPI (abiraterone or enzalutamide) and AAA617 and ARPI (abiraterone or enzalutamide). Condition PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy Phase Phase1, Phase2 Overall Status Recruiting Number of Participants123 Start Date Dec 05, 2025 Completion Date Sep 13, 2029 Gender Male Age(s) 18 Years - (Adult, Older Adult) ## Interventions Radiation ### AAA617 PSMA-targeted radiopharmaceutical Drug ### Abiraterone Androgen receptor pathway inhibitor Drug ### AMO959 DNA Damage Response inhibitor Drug ### Enzalutamide Androgen receptor pathway inhibitor ## Eligibility 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. 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