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Phase Ib/II Study of AMO959 with AAA617 and ARPI for PSMA-positive mCRPC

This study is for men with metastatic castration-resistant prostate cancer (mCRPC), meaning their cancer has spread and is no longer responding to standard hormone therapy. You might be eligible if your cancer has a specific marker called PSMA and you've already tried one type of hormone therapy (ARPI). Researchers are testing a new drug, AMO959 (a DNA damage response inhibitor), in combination with AAA617 (a PSMA-targeted radiopharmaceutical) and an existing ARPI like Enzalutamide or Abiraterone. The main goals are to see how safe this combination is, what side effects it might cause, and how well it works to treat the cancer. The study plans to enroll 123 participants.

Study design
This is an open-label, interventional study with two phases (Ib and II). Phase Ib will test different doses of AMO959 in a small group of participants, and Phase II will compare the combination treatment with AAA617 and ARPI alone in a larger group.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Safety will be assessed for up to approximately 45 months after starting treatment. Dose adjustments will be monitored for up to approximately 24 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07226986

A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA-positive mCRPC

Recruiting
PHASE1Ages 18+InterventionalTreatment
Novartis Pharmaceuticals
~123 participants
Updated 2026-08-18 on ClinicalTrials.gov
What's tested:AMO959AAA617EnzalutamideAbiraterone

At a glance

Recruiting sites
22 of 22 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase Ib: Incidence rate of Dose-limiting toxicities (DLTs)
Measured over Up to 42 days after the first AAA617 dose administration
+5 more outcomes measured

Conditions

PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy

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Prostate Carcinoma

Where it's being run

22 sites across 15 states
France4
Victoria3
Germany2
Spain2
California1
Texas1
Utah1
Western Australia1

Study leadership

  • Novartis Pharmaceuticals · STUDY_DIRECTOR · Novartis Pharmaceuticals

Who to contact

Novartis Pharmaceuticals
[email protected]
1-888-669-6682
Email the study team

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Eligibility criteria

Inclusion

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).

Exclusion

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.

What this trial measures

  • Phase Ib: Incidence rate of Dose-limiting toxicities (DLTs)Up to 42 days after the first AAA617 dose administration

    Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the evaluation period and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading.

  • Phase Ib: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)From date of start of study treatment, assessed up to approximately 45 months

    Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

  • Phase Ib: Number of Participants with dose adjustmentsFrom date of start of study treatment, assessed up to approximately 24 months

    The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation).

  • Phase Ib: Dose IntensityFrom date of start of study treatment, assessed up to approximately 24 months

    Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity).

  • Phase Ib: Duration of exposure to each study drugFrom date of start of study treatment, assessed up to approximately 24 months

    Duration of exposure (in months) to each study drug.

  • Phase II: Biochemical Response (PSA50)From date of start of study treatment, assessed up to approximately 24 months

    Biochemical response (PSA50), defined as the proportion of participants who achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥ 4 weeks later.