Recruiting

Phase 1

Phase 2

AMO959, AAA617, ARPIA 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

Sponsor:

Novartis Pharmaceuticals

Code:

NCT07226986

Conditions

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

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

AMO959

AAA617

Enzalutamide

Abiraterone

Study Details

Brief summary:

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.

Conditions

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

Study ID

NCT07226986

Start date

Dec 5, 2025

Status verified date

Aug, 2026

Completion date

Sep 13, 2029

Anticipated

Primary completion date

Jul 10, 2028

Anticipated

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

123 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: Phase II: Arm 2

experimental: 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.

Interventions

AMO959

DNA Damage Response inhibitor

AAA617

PSMA-targeted radiopharmaceutical

Enzalutamide

Androgen receptor pathway inhibitor

Abiraterone

Androgen receptor pathway inhibitor

Primary outcome measure

Phase Ib: Incidence rate of Dose-limiting toxicities (DLTs) [ Time Frame: Up to 42 days after the first AAA617 dose administration ]
Phase Ib: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From date of start of study treatment, assessed up to approximately 45 months ]
Phase Ib: Number of Participants with dose adjustments [ Time Frame: From date of start of study treatment, assessed up to approximately 24 months ]
Phase Ib: Dose Intensity [ Time Frame: From date of start of study treatment, assessed up to approximately 24 months ]
Phase Ib: Duration of exposure to each study drug [ Time Frame: From date of start of study treatment, assessed up to approximately 24 months ]
Phase II: Biochemical Response (PSA50) [ Time Frame: From date of start of study treatment, assessed up to approximately 24 months ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

1-888-669-6682 novartis.email@novartis.com

Novartis Pharmaceuticals

+41613241111 novartis.email@novartis.com

Locations

VA Greater LA Healthcare System

Recruiting

Los Angeles, California, United States, 90073

Contacts

Samantha Tran

Samantha.Tran@va.gov

Principal Investigator:

Matthew Rettig

Rio Grande Urology

Recruiting

El Paso, Texas, United States, 79912

Contacts

Paola Delgado

pdelgado@riograndeurology.com

Principal Investigator:

Jameson T Mendel

Utah Intermountain Medical Center

Recruiting

Murray, Utah, United States, 84107

Contacts

Preston Mayer

801-507-9333 preston.mayer@imail.org

Principal Investigator:

Dustin Boothe

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Aug 18, 2026

Last verified

Aug, 2026

Keywords

PSMA-positive metastatic castration resistant prostate cancer
AMO959
Lutetium (177Lu) vipivotide tetraxetan
Androgen Receptor Pathway Inhibitor (ARPI)
dose escalation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-08-18.