In the Prostate, Testicular, Penile Poster session at the 2021 American Society of Clinical Oncology 2021 Annual Meeting held on Friday June 4th, 2021, Dr. Chi presented the design of the SPLASH trial which seeks to prospectively evaluate the efficacy of 177Lu-PNT2002 for men with progressive mCRPC after androgen receptor axis-targeted (ARAT) therapy.
The Study evaluating metastatic castrate-resistant Prostate cancer using 177LU-PNT2002 PSMA therapy After Second line Hormonal treatment (SPLASH) (NCT04647526), is a multi-center, open-label, phase III study.
Eligible patients must be at least 18 years of age and have documented progressive mCRPC. Patients must have previously received only one androgen receptor axis-targeted therapy (in either the CSPC or CRPC setting) but not have received chemotherapy for CRPC and unfit or unwilling to receive chemotherapy. Patients must also have performance status of 0 or 1.
In addition, patients had to have high PSMA expression by PSMA PET/CT per blinded independent central review (BICR).
Patients are excluded for any prior cytotoxic chemotherapy for CPRC. However, those who received chemotherapy for hormone-sensitive disease is allowed, assuming that the last dose is at least 1 year prior to chemotherapy. Additionally, patients are excluded if they have liver metastases measuring 1cm or greater, a superscan on bone scan, CNS metastases, or contraindications to the use of planned androgen receptor antagonist therapy (ARAT).
The initial portion of the study will involve a 25-patient dosimetry lead-in. In this phase, patients will receive up to four cycles of 177Lu-PNT2002 at 6.8 GBq every 8 weeks. Following initial safety and preliminary efficacy evaluation during the dosimetry portion of the study, it will continue to the randomization phase in which approximately 390 patients will be randomized in a 2:1 ratio to receive 177Lu-PNT2002 (Arm A) versus enzalutamide or abiraterone (with prednisone or dexamethasone) (Arm B). This sample size will allow for 90% power to test the alternative hypothesis of a hazard ratio (HR) ≤ 0.66 at an α of 0.025 for the primary endpoint of radiologic progression-free survival (rPFS) assessed by BICR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria. In addition, a number of key secondary endpoints will be examined including objective response rate, duration of response, PSA response, biochemical PFS, overall survival, and safety and tolerability.
For patients randomized to Arm B, cross-over to 177Lu-PNT2002 treatment will be offered at the time of BICR-assessed radiologic progression.
The SPLASH trial is currently enrolling patients in Canada and the United States.
Presented by: Kim Chi, MD, medical oncologist, a senior research scientist, professor of medicine at the University of British Columbia
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Contact: @WallisCJD on Twitter at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021