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
PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy
Investigational drug(s) / intervention(s)
AMO959AAA617EnzalutamideAbiraterone
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
Sex
MALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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