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
NCT ID: NCT07226986
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE1/PHASE2
123 participants
INTERVENTIONAL
2025-12-16
2029-08-10
Brief Summary
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Detailed Description
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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).
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase 1b: Doublet
Participants will receive AMO959 BID for first 14 days followed by AAA617+AMO959 every 6 weeks for a maximum of 6 cycles.
AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Phase 1b: Triplet
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Enzalutamide
Androgen receptor pathway inhibitor
Abiraterone
Androgen receptor pathway inhibitor
Phase 1b: Food Effect
Participants will receive a single dose of AMO959 on Day 1 (fed), followed by 2-day washout, then AMO959 BID (fasted) for 14 days followed by 2-day washout and AAA617+AMO959 (fasted) every 6 weeks for a maximum of 6 cycles.
AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Phase II: Arm 1
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide administered continuously starting on day 1.
AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Enzalutamide
Androgen receptor pathway inhibitor
Abiraterone
Androgen receptor pathway inhibitor
Phase II: Arm 2
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Enzalutamide
Androgen receptor pathway inhibitor
Abiraterone
Androgen receptor pathway inhibitor
Phase II: Arm 3
Participants will receive AAA617 every 6 weeks for a maximum of 6 cycles, with ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
AAA617
PSMA-targeted radiopharmaceutical
Enzalutamide
Androgen receptor pathway inhibitor
Abiraterone
Androgen receptor pathway inhibitor
Interventions
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AMO959
DNA Damage Response inhibitor
AAA617
PSMA-targeted radiopharmaceutical
Enzalutamide
Androgen receptor pathway inhibitor
Abiraterone
Androgen receptor pathway inhibitor
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 Criteria
* 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.
18 Years
MALE
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Central Contacts
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Other Identifiers
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2025-521859-23-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
CAMO959A12103
Identifier Type: -
Identifier Source: org_study_id