FDA Grants Fast Track Designation to 177Lu-PNT2002 for mCRPC

Jean-Claude Provost, MD

The FDA has granted a fast track designation to ¹⁷⁷Lu-PNT2002 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).¹

¹⁷⁷Lu-PNT2002 is a prostate-specific membrane antigen (PSMA)–targeted, ¹⁷⁷Lu-based radiopharmaceutical therapy combining a PSMA-targeted ligand (PSMA-I&T) with the beta-emitting radioisotope no-carrier-added ¹⁷⁷Lu.

“Fast track designation by the FDA is an important milestone and recognizes the potential for ¹⁷⁷Lu-PNT2002 to address the significant unmet need for [patients with] mCRPC,” Jean-Claude Provost, MD, chief medical officer at Lantheus Holdings, stated in a news release. “We are encouraged by the FDA’s decision as it reflects the need for FDA approved and widely available treatments for these patients. This designation will allow us to work closely with the FDA, along with our partner POINT [Biopharma], to quickly advance ¹⁷⁷Lu-PNT2002, with the potential to make a meaningful difference for patients who require new treatment options.”

¹⁷⁷Lu-PNT2002 is currently being evaluated in the phase 3 SPLASH trial (NCT04647526), which is comparing the radioligand therapy vs abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who progressed following androgen receptor (AR)–targeted therapy.² Enrollment is complete, and topline data are expected to read out in the second half of 2023.¹

The multicenter, randomized, open-label study enrolled patients at least 18 years of age with histologically, pathologically, and/or cytologically confirmed prostate adenocarcinoma who are ineligible or adverse to chemotherapeutic treatment options.² Progression on prior AR-targeted therapy could have occurred in the castration-sensitive or castration-resistant setting. Other key inclusion criteria included 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 independent of transfusion.

Key exclusion criteria included prostate cancer with known significant sarcomatoid, spindle cell, or neuroendocrine components in more than 10% of present cells, prior treatment for prostate cancer within 28 days of randomization, any prior cytotoxic chemotherapy for CRPC, prior treatment with systemic radionuclides, prior immunotherapy (except for sipuleucel-T [Provenge]), prior PSMA-targeted radioligand therapy, or prior PARP inhibitor treatment for prostate cancer. Patients who progressed on 2 or more lines of AR-targeted therapy were excluded. Prior chemotherapy for hormone-sensitive prostate cancer was allowed if the last dose was administered more than 1 year prior to enrollment.

Patients were randomly assigned to receive 6.8 GBq (±10%) of ¹⁷⁷Lu-PNT2002 once every 8 weeks for 4 cycles in the experimental arm, or abiraterone or enzalutamide in the control arm. The abiraterone regimen consisted of 1000 mg of oral abiraterone once per day with 5 mg of prednisone twice per day or 0.5 mg of dexamethasone once per day. Enzalutamide was given orally at 160 mg once per day.

Radiographic progression-free survival (rPFS) served as the trial’s primary end point. Secondary end points consisted of objective response rate, duration of response, overall survival, PSA response, biochemical PFS, and safety/tolerability.

“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.¹ “We are seeing that radioligand therapy is quickly becoming another pillar of cancer treatment, and, with our continued focus on supply chain excellence, 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.”

References

1. Lantheus and POINT Biopharma announce FDA grants fast track designation for ¹⁷⁷Lu-PNT2002 for the treatment of metastatic castration resistant prostate cancer. News release. April 24, 2023. Accessed April 25, 2023. https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-and-point-biopharma-announce-fda-grants-fast-track
2. Study evaluating mCRPC treatment using PSMA [Lu-177]-PNT2002 therapy after second-line hormonal treatment (SPLASH). ClinicalTrials.gov. Updated March 31, 2023. Accessed April 25, 2023. https://www.clinicaltrials.gov/ct2/show/NCT04647526