Lantheus may have been hoping that “statistically significant” phase 3 data for its radioligand therapy would make a splash at ESMO, but not everyone is impressed.
The biotech used the European Society for Medical Oncology Congress (ESMO) over the weekend to unveil the latest data from its SPLASH study of Lu-PNT2002. The prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is being evaluated in patients with metastatic castration-resistant prostate cancer (mCRPC) who had already tried an androgen receptor pathway inhibitor (ARPI).
The 412-person study showed an overall response rate of 38.1% for Lu-PNT2002 compared to 12% who only received an ARPI, Lantheus said. The biotech already reported in December 2023 that the study had hit its primary endpoint of demonstrating a median radiographic progression-free survival (rPFS) of 9.5 months for patients treated with Lu-PNT2002, compared to six months for those on an ARPI.
But after reviewing the ESMO data, analysts at William Blair said their view was that opportunities to use Lu-PNT2002 would be “significantly limited” to situations where Novartis’ approved radiotherapy Pluvicto is not available.
The analysts namechecked the phase 3 PSMAfore trial of Pluvicto, which had shown an objective response rate of 51% compared to 38% for Lu-PNT2002 in the SPLASH study. And while the overall survival rates have been “subject of ongoing debate in the investment community,” the analysts referred to an overall survival hazard ratio over the control arm of 1.11 for Lu-PNT2002 compared to 1.16 for Pluvicto.
The SPLASH trial saw Lu-PNT2002 administered at 6.8 GBq every eight weeks for up to four cycles, and the analysts said it was “perhaps a surprise” that despite reducing the maximum cumulative dose of Lu-PNT2002 to 27.2 GBq compared to 44.4GBq for Pluvicto in the PSMAfore trial, this “did not confer tolerability advantages over Pluvicto.”
“Taken together, it is our view that PNT2002 is unlikely to disrupt the radioligand market dynamic due to inferior clinical efficacy and comparable tolerability versus Pluvicto, and Pluvicto could continue to command market leadership in the post-novel hormone therapy mCRPC setting following the potential approval, based on the positive phase 3 PSMAfore study,” the analysts added.
Despite the analysts’ downbeat assessment, Oliver Sartor, M.D., Director of Radiopharmaceutical Trials and Professor of Medical Oncology at the Mayo Clinic in Rochester, Minnesota, used Lantheus’ Sept. 15 release to say he was “encouraged” by the SPLASH data.
“Lu-PNT2002 demonstrat[ed] improvement compared to ARPI change in radiographic progression-free survival, positive interim crossover-adjusted overall survival hazard ratios, as well as improved quality of life,” Sartor added. “These initial data underscore the importance of PSMA-targeted RLTs, including Lu-PNT2002, as potential treatment options for patients who have limited choices after progressing on ARPI therapy.”
Lantheus bought Lu-PNT2002 from POINT Biopharma in 2022 as part of a $260 million upfront deal. Lantheus Chief Medical Officer Jeff Humphrey, M.D., said yesterday’s interim analysis had shown that Lu-PNT2002 “is outperforming the control arm and showing an improved quality of life for patients.”