POINT Biopharma & Lantheus Announce Positive Topline Results From Pivotal SPLASH Trial in Metastatic Castration-Resistant Prostate Cancer

POINT Biopharma Global Inc. and Lantheus Holdings, Inc. recently announced statistically significant topline results from the pivotal Phase 3 SPLASH study evaluating the efficacy and safety of ¹⁷⁷Lu-PNT2002, a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), in patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on an androgen receptor pathway inhibitor (ARPI).

“There is an urgent unmet need for targeted treatment options for mCRPC patients, particularly for those whose cancer has progressed on androgen receptor pathway inhibitors,” said Dr. Kim Chi, SPLASH Principal Investigator, Medical Oncologist, BC Cancer. “The SPLASH study results demonstrate that ¹⁷⁷Lu-PNT2002 is well-tolerated and has the potential to play an important role in addressing those needs for patients with chemotherapy-naïve mCRPC.”

The SPLASH trial met its primary endpoint, demonstrating a median radiographic progression-free survival (rPFS) per blinded independent central review of 9.5 months for patients treated with ¹⁷⁷Lu-PNT2002, compared to 6.0 months for patients treated with ARPI in the control arm, a statistically significant 29% reduction in the risk of radiographic progression or death (hazard ratio [HR] 0.71; p=0.0088). At the time of the analysis, interim overall survival (OS) results were immature (46% of protocol-specified target OS events reached), the HR was 1.11. The companies expect additional, follow-up data in 2024 prior to the potential submission of a New Drug Application (NDA).

¹⁷⁷Lu-PNT2002 demonstrated a favorable safety profile with grade ≥3 treatment-emergent adverse events (TEAEs) per Common Terminology Criteria for Adverse Events (CTCAE), serious TEAEs, and TEAEs leading to discontinuation occurring at lower rates in the ¹⁷⁷Lu-PNT2002 arm than in the ARPI arm (30.1%, 17.1%, and 1.9% vs. 36.9%, 23.1%, and 6.2%, respectively).

The open-label study randomized 412 patients with PSMA-expressing mCRPC who had progressed on ARPI therapy and either refused or were not eligible for chemotherapy, in a 2:1 randomization ratio (¹⁷⁷Lu-PNT2002: control group). At the time of the analysis, 84.6% of patients who experienced progressive disease in the control arm subsequently crossed over to receive ¹⁷⁷Lu-PNT2002. SPLASH was conducted across the United States, Canada, Europe, and the United Kingdom. Eighty percent of SPLASH patients resided in North America and approximately 10% of all participants were Black or African American.

“The success of ¹⁷⁷Lu-PNT2002 in this trial demonstrates the value of treating patients with radioligand therapy at this stage of the disease continuum. With only four treatment administrations over a 32-week period, this regimen provides reduced treatment intensity compared to the control arm, while also delaying disease progression with lower toxicity,” said Neil Fleshner, MD, Co-founder and Chief Medical Officer at POINT Biopharma. “We extend our deepest gratitude to the SPLASH study participants and their families and caregivers, as well as the investigators and their hard-working staff.”

“We are encouraged by the results of the SPLASH trial, which showed the benefits that ¹⁷⁷Lu-PNT2002 offers to patients with mCRPC. We are proud to be at the forefront of advancing the potential of targeted RLT with ¹⁷⁷Lu-PNT2002. As the leading radiopharmaceutical-focused company, we are committed to providing clinicians with cutting-edge options to fight disease and improve patient outcomes,” said Jean-Claude Provost, MD, Chief Medical Officer at Lantheus. “We look forward to sharing additional data in the future, and to collaborating with regulatory authorities and POINT Biopharma to bring this promising therapy to the prostate cancer patient community.”

Full SPLASH trial results will be presented at a future medical congress.

The Phase 3 SPLASH trial is a multicenter, randomized, open label assessment of ¹⁷⁷Lu-PNT2002 in patients with PSMA-expressing mCRPC who have progressed on ARPI therapy and refuse, or are not eligible for, chemotherapy. The randomization phase of the study randomized 412 patients across North America, Europe, and the United Kingdom. Patients were randomized 2:1 with those in arm A receiving ¹⁷⁷Lu-PNT2002 and those in arm B receiving either abiraterone or enzalutamide. Patients in arm B who experience centrally assessed radiographic progression and meet protocol eligibility have the option to crossover and receive ¹⁷⁷Lu-PNT2002. Patients will be followed for up to 5 years from their first ¹⁷⁷Lu-PNT2002 dose. The primary endpoint of the study is radiographic progression-free survival. More information about the trial is accessible at www.ClinicalTrials.gov, identifier NCT04647526.

¹⁷⁷Lu-PNT2002 is a PSMA-targeted, lutetium 177-based radioligand therapy candidate that combines a PSMA-targeted ligand, PSMA-I&T, with the beta-emitting radioisotope no-carrier-added lutetium-177. Lantheus Holdings, Inc. in-licensed exclusive worldwide commercialization rights (excluding certain Asian territories) to ¹⁷⁷Lu-PNT2002 from POINT in December of 2022. In April of 2023, the FDA granted Fast Track designation for ¹⁷⁷Lu-PNT2002 for the treatment of mCRPC. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and address unmet medical needs.

Prostate cancer is the second most common form of cancer affecting men in the US – an estimated 1 in 8 men will be diagnosed with prostate cancer in their lifetimes. The American Cancer Society estimates that in 2023, almost 288,300 new cases of prostate cancer will be diagnosed, and about 34,700 men will die of the disease.

Lantheus is the leading radiopharmaceutical-focused company, delivering life-changing science to enable clinicians to Find, Fight and Follow disease to deliver better patient outcomes. Headquartered in Massachusetts with offices in New Jersey, Canada, and Sweden, Lantheus has been providing radiopharmaceutical solutions for more than 65 years. For more information, visit www.lantheus.com.

POINT Biopharma Global Inc. is a globally focused radiopharmaceutical company building a platform for the clinical development and commercialization of radioligands that fight cancer. POINT aims to transform precision oncology by combining a portfolio of targeted radioligand assets, a seasoned management team, an industry-leading pipeline, in-house manufacturing capabilities, and secured supply for medical isotopes including actinium-225 and lutetium-177. For more information, visit https://www.pointbiopharma.com/.