177Lu-PNT2002 shows initial safety and efficacy in mCRPC

Topline results from the phase 3 SPLASH trial (NCT04647526) show initial safety and efficacy of 177Lu-PNT2002, an investigational prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed following treatment with androgen receptor pathway inhibitor (ARPI), according to a joint news release from Lantheus and POINT Biopharma.¹

"With only 4 treatment administrations over a 32-week period, this regimen provides reduced treatment intensity compared [with] the control arm, while also delaying disease progression with lower toxicity,” says Neil Fleshner, MD.

According to the release, the trial met its primary end point of radiographic progression-free survival (rPFS) per blinded independent central review and demonstrated a favorable safety profile in this patient population.

“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 principal investigator and medical oncologist at BC Cancer Kim Chi, MD, FRCPC, in the news release.¹ “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.”

Overall, 177Lu-PNT2002 demonstrated a median rPFS of 9.5 months, compared with 6.0 months among patients in the control arm, who were treated with an ARPI. This translates to a 29% reduction in the risk of radiographic progression or death with 177Lu-PNT2002 (HR, 0.71; P = .0088).

Results from the key secondary outcome measure of overall survival (OS) were immature at the time of analysis, with 46% of pre-specified target OS events reached (HR, 1.11).

Regarding safety, 30.1% of patients in the 177Lu-PNT2002 arm experienced grade 3 or higher adverse events (AEs), compared with 36.9% among patients who received an ARPI. Serious treatment-emergent adverse events (TEAEs) were experienced among 17.1% of patients in the 177Lu-PNT2002 arm, compared with 23.1% in the ARPI arm. Overall, 1.9% of patients who received 177Lu-PNT2002 discontinued treatment due to TEAEs, vs 6.2% among patients in the ARPI cohort.

"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 4 treatment administrations over a 32-week period, this regimen provides reduced treatment intensity compared [with] the control arm, while also delaying disease progression with lower toxicity,” said Neil Fleshner, MD, co-founder and Chief Medical Officer at POINT Biopharma, in the news release.¹ “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."

Overall, the open-label SPLASH trial included 412 patients with PSMA-expressing mCRPC who were randomized 2:1 to receive 6.8 GBq 177Lu-PNT2002 every 8 weeks for 4 cycles or an ARPI, being either 1000 mg oral abiraterone (Zytiga) once daily (with 5 mg prednisone twice daily or 0.5 mg dexamethasone once daily) or 160 mg oral enzalutamide (Xtandi) once daily.² All patients had progressed on ARPI therapy and either refused or were not eligible for chemotherapy. Patients were treated across centers in the United States, Canada, Europe, and the United Kingdom.

At the time of data report, 84.6% of the patients in the ARPI group who experienced disease progression subsequently crossed over to receive 177Lu-PNT2002.

According to the news release, additional data from the trial is expected in 2024, which may support the submission of a new drug application to the FDA, pending further positive results. Full results from the trial are expected to be presented at an upcoming medical meeting.

References

1. Lantheus and POINT Biopharma announce positive topline results from pivotal SPLASH trial in metastatic castration-resistant prostate cancer. News release. Lantheus Holdings and POINT Biopharma Global. December 18, 2023. Accessed December 19, 2023. https://www.pointbiopharma.com/press-releases/splash-topline-results

2. Study evaluating mCRPC treatment using PSMA [LU-177]-PNT2002 therapy after second-line hormonal treatment (SPLASH). ClinicalTrials.gov. Last updated November 2, 2023. Accessed December 19, 2023. https://clinicaltrials.gov/study/NCT04647526