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.
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.
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
Sequential
AMO959
DrugDNA Damage Response inhibitor
AAA617
RadiationPSMA-targeted radiopharmaceutical
Enzalutamide
DrugAndrogen receptor pathway inhibitor
Abiraterone
DrugAndrogen receptor pathway inhibitor
6
Treatment groupsSee each treatment group below.
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.
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.
Phase Ib: Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation).
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).
Prostate Specific Antigen 90 (PSA90) response
PSA90 response is defined as the proportion of participants who have achieved a ≥ 90% 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.
Phase Ib: Prostate Specific Antigen 50 (PSA50) response
PSA50 response is defined as the proportion of participants who have achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to the start of new anti-cancer therapy, confirmed by a second PSA measurement ≥4 weeks later.
Phase Ib and Phase II: Radiographic progression-free survival (rPFS)
Radiographic progression- free survival (rPFS) is defined as the time from the date of start of study treatment (Phase Ib) / randomization (Phase II) to the date of first documented radiographic disease progression using conventional imaging and Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 criteria (Scher et al 2016) or death due to any cause, whichever occurs first.
Phase Ib and Phase II: Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue based on tumor response data and according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3.
Click on the lead sponsor to view all of their trials.
