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

Condition(s) studied

Investigational drug(s) / intervention(s)

AMO959: DNA Damage Response inhibitor

AAA617: PSMA-targeted radiopharmaceutical

Enzalutamide: Androgen receptor pathway inhibitor

Abiraterone: Androgen receptor pathway inhibitor

Study 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.

Eligibility

Primary outcome measure(s)

• 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 adjustments — From 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 Intensity — From 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 drug — From 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.

Trial sites (23)

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