FDA Fast Tracks 177Lu-PNT2002 for the Treatment of mCRPC


The FDA continues to push forward PSMA-targeted therapies to address unmet needs for patients with metastatic castration-resistant prostate cancer.

The FDA has granted fast track designation to the prostate specific membrane antigen (PSMA)-targeted therapy, 177Lu-PNT2002, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).1

The 177Lu-based radiotherapy works by combining the PSMA-targeted ligand, PSMA I&T with the beta-emitting radioisotope 177Lu. The mechanism has been shown preclinically to produce high radiographic and biochemical response rate and low toxicity.

In the phase 3 VISION study (NCT03511664) of 177Lu-PSMA-617 in patients with mCRPC, a median progression-free survival (PFS) of 8.7 months, and median overall survival (OS) of 15.3 months was shown, along with a radiographic response rate of 9.2%.2 VISION led to the FDA approval 177Lu-PSMA-617 as the first tumor-targeted radionuclide therapy to be offered commercially.

“With the approval of targeted radiotherapy is now a reality in prostate cancer. And this has come about because PSMA is just such a terrific target. Almost all of it is on prostate cancer cells. There is some in physiologic spaces, but otherwise, it just makes for a very nice target. And with both investigational drugs and those that are now approved, we have had some real successes,” Jones T. Nauseef, MD, PhD, assistant professor of Medicine, Division of Hematology and Medical Oncology, Weil Cornell Medicine and attending physician, NewYork-Presbyterian Hospital told Targeted OncologyTM, in an interview.

About the Phase 2 SPLASH Study

Trial Name: A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)

ClinicalTrials.gov Identifier: NCT04647526

Sponsor: POINT Biopharma

Recruitment Contact: Richard Cioci+, 1-833-544-2637 ext 202, SPLASH@pointbiopharma.com

Completion Date: March 2028

177Lu-PNT2002 will be investigated in the phase 3 SPLASH trial (NCT04647526), a multicenter, randomized, open-label study that will include approximately 415 patients with mCRPC.1 The goal of the study is to assess the efficacy and safety of 177Lu-PNT2002 in this patient population following treatment with an androgen receptor inhibitor. Commencement of the study will include 25 patients who will be evaluated for safety and dosimetry, followed by 2:1 randomization of 390 patients to an experimental arm of 177Lu-PNT2002 or the comparator arm of abiraterone (Zytiga), prednisone or dexamethasone, or enzalutamide (Xtandi).3

Patients in the experimental arm will be administered 6.8 GBq of 177Lu-PNT2002 every 8 weeks for 4 cycles. Those in the comparator arm will receive 1000 mg of oral abiraterone once daily (QD) with 0.5 mg of prednisone or dexamethasone QD, or enzalutamide 160 mg QD.

The primary end point to be explored during the study is radiographic PFS per RECIST v1.1. The secondary end points include objective response rate, duration of response, OS, prostate specific antigen response, and biochemical PFS. The study will also evaluate the safety of 177Lu-PNT2002 based on the frequency and severity of adverse events, which will be graded and categorized using the Common Terminology Criteria for Adverse Events v5.0.

prostate cancer under microscope, prostate tumor, PC-3 human prostate cancer cells | Image Credit © heitipaves  - [stock.adobe.com]

Image Credit © heitipaves [stock.adobe.com]

To be eligible for inclusion in the study, patients must be 18 years of age or older with a histological, pathological, or cytological confirmation for mCRCP, show PSMA on a PET scan, have adequate organ function, an ECOG performance status of 0 or 1, and proper castrate circulating testosterone levels. Patients are also required to be ineligible for chemotherapy, have progressive disease, progressed on prior treatment with either abiraterone, enzalutamide, darolutamide (Nubeqa), or apalutamide (Erleada) in either the CRPC or castration sensitive prostate cancer setting.

The study will exclude patients who were previously treated with cytotoxic chemotherapy for CRPC within a year, systemic radionuclides, immunotherapy, excluding sipuleucel-T (Provenge), PSMA-targeted radioligand therapy, PARP inhibitor, bone-targeted therapy, major surgery within 30 days of randomization, or more than 2 lines of prior abiraterone, enzalutamide, darolutamide, or apalutamide. Patients will also be ineligible for the study if their life expectancy is less than 6 months, or they have an infection or illness that may interfere with the effectiveness of study treatment.

“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,” said Neil Fleshner, MD, chief medical officer, POINT Biopharma, in a press release.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.”


  • 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 and POINT Biopharma. April 24, 2023. Accessed April 25, 2023. https://bit.ly/3ALtKZv
  • Sartor O, de Bono J, Chi Km, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385(12):1091-1103. doi:10.1056/NEJMoa2107322

Rahbar K, Ahmadzadehfar H, Kratochwil C et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med 2017; 58: 85–90. doi:10.2967/jnumed.116.183194

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