The phase 3 SPLASH trial will assess the benefit of 177Lu-PNT2002 in patients with PSMA-expressing metastatic castration-resistant prostate cancer.
The FDA has granted fast track designation to 177Lu-PNT2002 as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), according to a press release from developer Lantheus Holdings.
The radiotherapeutic is being assessed as part of the multi-center, open-label randomized phase 3 SPLASH trial (NCT04647526) in a population of patients with prostate-specific membrane antigen (PSMA)-expressing mCRPC who had progressed following treatment with an androgen receptor inhibitor, and refused or were ineligible for treatment with chemotherapy.
177Lu-PNT2002 is a PSMA–targeted radiopharmaceutical therapy that merged a PSMA-targeted ligand PSMA I&T and beta-emitting radioisotope no-carrier added 177Lu.
“We are encouraged by the FDA’s decision as it reflects the need for FDA-approved and widely available treatments for these patients,” Jean-Claude Provost, MD, chief medical officer at Lantheus, said in the press release. “This designation will allow us to work closely with the FDA, along with our partner POINT, to quickly advance 177Lu-PNT2002, with the potential to make a meaningful difference for patients who require new treatment options.”
Patients who enrolled on the study were randomly assigned 2:1 to receive either 177Lu-PNT2002 in arm A or abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in arm B. Those in arm B who experience centrally assessed radiographic progression and met protocol eligibility criteria may crossover and be treated with 177Lu-PNT2002.
The trial population will be followed for up to 5 years following treatment with the radiotherapeutic.
Primary study end points included radiographic progression-free survival, with key secondary end points including overall survival, overall response rate, and duration of response. Safety and tolerability will also be examined.
Study enrollment has been completed and topline data are anticipated for the second half of 2023.
The trial has an estimated enrollment of 415 patients who will be treated with either 6.8 GBq of 177Lu-PNT2002 every 8 weeks for 4 cycles, or 1000 mg of oral abiraterone daily plus 160 mg of oral enzalutamide daily.
The study includes patients 18 years of age or older with histological, pathologic, and/or cytologically confirmed prostate adenocarcinoma. Moreover, patients needed to be ineligible or not able to receive chemotherapy, as well as have progressive disease. Patients also needed to have a positive PSMA PET scan, castrate circulating testosterone levels of less than 1.7 nmol/L or less than 50 ng/dL, and adequate organ function.
An ECOG performance status of 0 to 1 was also required.
Patients with significant sarcomatoid or spindle cells or neuroendocrine components were not eligible for treatment. Additionally, patients could not be enrolled if they had previous treatment for prostate cancer within 28 days or less of randomization, or any prior treatment with cytotoxic chemotherapy. Moreover, prior treatment with systemic radionucleotides, immunotherapy, PSMA radioligand therapy, or PARP inhibitors was not permitted.
Those with major surgery 30 days or less from randomization, an estimated life expectancy of less than 6 months, or the presence of liver metastases over 1 cm on imaging were not able to enroll on the SPLASH study.
“The FDA Fast Track designation for 177Lu-PNT2002 underscores its potential to address a serious unmet need and serve as a meaningful therapeutic option for patients with mCRPC,” Neil Fleshner, MD, chief medical officer of POINT Biopharma, said in the press release. “We believe that we are very well positioned to meet market demands post-approval. We will continue to work closely with our partner Lantheus and with the FDA to bring 177Lu-PNT2002 to patients as quickly as possible.”
Lantheus and POINT Biopharma announce FDA grants fast track designation for 177Lu-PNT2002 for the treatment of metastatic castration resistant prostate cancer. News release. Lantheus Holdings. April 24, 2023. Accessed April 24, 2023. https://bit.ly/40DauaV