ESMO 2023 is around the corner, and major pharmaceutical companies such as Amgen, Novartis, Janssen, and Merck are gearing up for the conference, prepared to present data readouts and comprehensive analyses. In 2022, the total diagnosed prevalent population of metastatic castration-resistant prostate cancer (mCRPC) was approximately 60,000 in the United States. This content specifically focuses on Novartis' Phase III PSMAfore trial of PLUVICTO in the first-line setting. PLUVICTO has already received approval for treating adult patients with PSMA-positive mCRPC who have undergone androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer

• Abstract Number – #LBA13
• Abstract Type - Proffered Paper Session
• Indication – Metastatic Castration-resistant Prostate Cancer
• Technology - Radiotherapy

The preliminary results originate from the Phase III PSMAfore trial, where all subjects had previously received androgen-receptor inhibitor treatment but had not undergone taxane-based chemotherapy. This signifies a treatment phase preceding the existing FDA approval of Novartis' PLUVICTO, specifically indicated for metastatic castration-resistant prostate cancer (mCRPC) following chemotherapy.

Novartis reported successful outcomes from the Phase III PSMAfore trial involving PLUVICTO, meeting its primary endpoint. The drug exhibited a statistically significant and clinically meaningful enhancement in radiographic progression-free survival (rPFS) for patients with PSMA–positive metastatic castration-resistant prostate cancer (mCRPC) who had undergone androgen-receptor pathway inhibitor (ARPI) therapy, compared to a change in ARPI. PLUVICTO, currently approved as a post-chemotherapy drug mCRPC, the PSMAfore trial (NCT04689828) aims to position 177Lu-PSMA-617 as a first-line treatment in metastatic CRPC.

Novartis is optimistic about PLUVICTO's market share, as it garnered nearly USD 2.5 million in the US market in 2022. However, the company faces challenges due to prolonged manufacturing issues that could impact its plans. The positive outlook relies on favorable results from the PSMAfore trial and another Phase III trial, PSMAaddition, which is expected to release data for metastatic hormone-sensitive prostate cancer (mHSPC/mCSPC) next year. To prepare for the potential expansion of PLUVICTO and broader radiotherapy initiatives, Novartis is actively enhancing its production capabilities. This includes increasing capacity at its radioligand site in Millburn, New Jersey, following recent manufacturing challenges and a temporary production halt.

Additionally, the PSMAfore trial shows positive outcomes in radiographic progression-free survival (PFS), but the full clinical significance is still to be determined. The upcoming data presentation at ESMO 2023 holds the potential to broaden the application of PLUVICTO beyond its currently approved post-chemotherapy setting.