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

NCT07226986 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAMO959A121032025-521859-23-00
• Study Type: interventional
• Target: 123
• Locations: 5 countries
• Sites: 8

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Phase Ib: Incidence rate of Dose-limiting toxicities (DLTs)

  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.

  Up to 42 days after the first AAA617 dose administration

• Phase Ib: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

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

  From date of start of study treatment, assessed up to approximately 45 months

• Phase Ib: Number of Participants with dose adjustments

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

  From date of start of study treatment, assessed up to approximately 24 months

• Phase Ib: Dose Intensity

  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).

  From date of start of study treatment, assessed up to approximately 24 months

• Phase Ib: Duration of exposure to each study drug

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

  From date of start of study treatment, assessed up to approximately 24 months

• Phase II: Biochemical Response (PSA50)

  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.

  From date of start of study treatment, assessed up to approximately 24 months

Secondary Outcomes (20)

• Prostate Specific Antigen 90 (PSA90) response

  From date of start of study treatment, assessed up to approximately 24 months

• Phase Ib: Prostate Specific Antigen 50 (PSA50) response

  From date of start of study treatment, assessed up to approximately 24 months

• Phase Ib and Phase II: Radiographic progression-free survival (rPFS)

  From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months

• Phase Ib and Phase II: Overall Response Rate (ORR)

  From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months

• Phase Ib and Phase II: Disease control rate (DCR)

  From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months

Study Arms (6)

Phase 1b: Doublet

EXPERIMENTAL

Participants will receive AMO959 BID for first 14 days followed by AAA617+AMO959 every 6 weeks for a maximum of 6 cycles.

Drug: AMO959; Radiation: AAA617

Phase 1b: Triplet

EXPERIMENTAL

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.

Drug: AMO959; Radiation: AAA617; Drug: Enzalutamide; Drug: Abiraterone

Phase 1b: Food Effect

EXPERIMENTAL

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.

Drug: AMO959; Radiation: AAA617

Phase II: Arm 1

EXPERIMENTAL

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.

Drug: AMO959; Radiation: AAA617; Drug: Enzalutamide; Drug: Abiraterone

Phase II: Arm 2

EXPERIMENTAL

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.

Drug: AMO959; Radiation: AAA617; Drug: Enzalutamide; Drug: Abiraterone

Phase II: Arm 3

EXPERIMENTAL

Participants will receive AAA617 every 6 weeks for a maximum of 6 cycles, with ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.

Radiation: AAA617; Drug: Enzalutamide; Drug: Abiraterone

Interventions

AMO959 DRUG

DNA Damage Response inhibitor

Also known as: BY1298, BY101298

Phase 1b: Doublet; Phase 1b: Food Effect; Phase 1b: Triplet; Phase II: Arm 1; Phase II: Arm 2

AAA617 RADIATION

PSMA-targeted radiopharmaceutical

Also known as: Pluvicto [177Lu]Lu-PSMA-617

Phase 1b: Doublet; Phase 1b: Food Effect; Phase 1b: Triplet; Phase II: Arm 1; Phase II: Arm 2; Phase II: Arm 3

Enzalutamide DRUG

Androgen receptor pathway inhibitor

Phase 1b: Triplet; Phase II: Arm 1; Phase II: Arm 2; Phase II: Arm 3

Abiraterone DRUG

Androgen receptor pathway inhibitor

Phase 1b: Triplet; Phase II: Arm 1; Phase II: Arm 2; Phase II: Arm 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Rio Grande Urology

El Paso, Texas, 79912, United States

RECRUITING

Novartis Investigative Site

Malvern, Victoria, 3144, Australia

RECRUITING

Novartis Investigative Site

Murdoch, Western Australia, 6150, Australia

RECRUITING

Novartis Investigative Site

Clermont-Ferrand, 63011, France

RECRUITING

Novartis Investigative Site

Nantes, 44093, France

RECRUITING

Novartis Investigative Site

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

MeSH Terms

Interventions

Pluvicto; enzalutamide; abiraterone

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2025
• First Posted: November 12, 2025
• Study Start: December 5, 2025
• Primary Completion (Estimated): July 10, 2028
• Study Completion (Estimated): September 13, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); FR (2); US (1); JP (1); ES (2)