Overview
This Phase II study aims to evaluate the efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg QD doses + lutetium (177Lu) vipivotide tetraxetan (hereafter referred as AAA617) compared with AAA617 (control) in participants with metastatic Castration Resistant Prostate Cancer (mCRPC) with prior exposure to at least 1 Androgen Receptor Pathway Inhibitor (ARPI) and 0-2 taxane regimens and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and pharmacokinetic (PK) data from participants randomized in the study will be evaluated.
Description
The study consists of a screening period, a randomization period, a treatment period, a post-treatment safety follow-up followed by a long-term follow-up period.
JSB462 administration starts at day 1 of randomization, whereas AAA617 administration starts at day 1 of treatment period. Participants in arm 1 and arm 2 will therefore receive JSB462 during the 14-day randomization period before first administration of AAA617.
- JSB462 is administered orally, daily and continuously (100 mg or 300 mg once a day (QD)) until disease progression per Prostate Cancer Working Group (PCWG) 3-modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
- AAA617 will be administered at 7.4 gigabecquerel (GBq) intravenously every 6 weeks for up to 6 doses, unless there is disease progression per PCWG3-modified RECIST v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
During the post-treatment follow up period:
- Safety follow-Up: After discontinuation of study treatment, all participants will be followed for at least 1 safety follow-up visit (30 days [+/- 7 days] after end of treatment visit). Subsequent lines of therapy may be administered according to investigator's discretion after treatment discontinuation.
- Long-term follow-up: Starts after the Safety follow-up period and lasts until the end of study. Safety, efficacy and survival information may be collected from the participants during this period.
Eligibility
Key Inclusion Criteria:
- Adult male participants with histologically and/or cytologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade ≤2.
- At least 1 bone or visceral metastatic lesion present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to initiation of study treatment.
- Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive and eligible as determined by the sponsor's central reader.
- Participant must have prior exposure to at least one second generation ARPI in the metastatic/advanced setting.
- Previous treatment with a maximum of 2 taxane regimens is allowed.
- Participants eligible for PARPi and/or immune checkpoint inhibitor (per local testing and according to investigator's judgement) are eligible to participate if they have previous exposure to this(these) therapy(ies).
Key Exclusion Criteria:
- Prior treatment with any RLT (approved or investigational) is not allowed
- Prior treatment with a protein degrader compound that targets AR is not allowed
Other protocol-defined inclusion/exclusion criteria may apply.