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

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 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• AMO959 — DRUG
  DNA Damage Response inhibitor
• AAA617 — RADIATION
  PSMA-targeted radiopharmaceutical
• Enzalutamide — DRUG
  Androgen receptor pathway inhibitor
• Abiraterone — DRUG
  Androgen receptor pathway inhibitor

Study Details

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.

Key Dates

Start date

Dec 5, 2025

Status verified

Jun 2026

Primary completion

Jul 10, 2028

Completion

Sep 13, 2029

Study Design

Enrollment

123 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

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
  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 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.

Primary Outcome Measure

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

Central Contacts

• Novartis Pharmaceuticals
  1-888-669-6682
  [email protected]
• Novartis Pharmaceuticals
  +41613241111
  [email protected]

Locations (2)

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