FDA Expands Indication for Lutetium Lu 177 Vipivotide Tetraxetan in mCRPC

FDA

The FDA has expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.1.2

In March 2022, the radioligand therapy was approved by the FDA for the treatment of adult patients with PSMA-positive mCRPC who have previously received other anticancer therapies, such as AR pathway inhibition and taxane-based chemotherapy.3

Approval of the expanded indication was supported by data from the phase 3 PSMAfore trial (NCT04689828), which showed that in patients with PSMA-positive mCRPC who received prior treatment with an AR patheway inhibitor and were cosidered appropriate for delayed taxane-based chemotherapy, those given lutetium Lu 177 vipivotide tetraxetan (n = 234) achieved a median radiographic progression-free survival (rPFS) of 9.3 months (95% CI, 7-not estimable) vs 5.6 months (95% CI, 4-6) for those who switched to a different AR pathway inhibitor (n = 234; HR 0.41; 95% CI, 0.29-0.56; P < .0001).1,4

“The FDA’s expanded approval of [lutetium Lu 177 vipivotide tetraxetan] marks a transformative step forward in the treatment of mCRPC, underscoring the growing impact of precision oncology," Jorge A. Garcia, MD, a genitourinary medical oncologist and chair of the Solid Tumor Oncology Division at University Hospitals Seidman Cancer Center/Case Western Reserve University in Cleveland, Ohio, told OncLive®. "By enabling access to this targeted radioligand therapy prior to chemotherapy, we are not only broadening treatment options but also redefining the standard of care for PSMA-positive disease."

The FDA recommended that potential candidates for lutetium Lu 177 vipivotide tetraxetan should be selected using gallium Ga 68 gozetotide (Locametz) or another approved PSMA PET product based on PSMA expression in tumors.1 The radioactive diagnostic agent gallium Ga 68 gozetotide was approved by the FDA in 2022 in tandem with lutetium Lu 177 vipivotide tetraxetan.

The randomized, controlled, open-label, multicenter PSMAfore study enrolled 468 patients with PSMA-positive mCRPC who experienced disease progression on a prior AR pathway inhibitor.1 Patients were required to be considered appropriate candidates to delay taxane-based chemotherapy, per investigator discretion.

Investigators randomly assigned patients 1:1 to receive lutetium Lu 177 vipivotide tetraxetan at 7.4 GBq (200 mCi) once every 6 weeks for a total of 6 doses; or a change in AR pathway inhibitor. Patients in the control arm who experienced were allowed to cross over to receive lutetium Lu 177 vipivotide tetraxetan after disease progression.

The trial's primary end point was rPFS per blinded independent central review. Secondary end points comprised overall survival (OS) and safety.

Additional data showed that there was no statistically significant difference in OS. The median OS was 24.5 months (95% CI, 19.5-28.9) for lutetium Lu 177 vipivotide tetraxetan compared with 23.1 months (95% CI, 19.6-25.5) for an AR pathway inhibitor (HR, 0.91; 95% CI, 0.72-1.14). Notably, 60% of patients randomly assigned to the control arm crossed over to receive lutetium Lu 177 vipivotide tetraxetan following disease progression.

Regarding safety, data for lutetium Lu 177 vipivotide tetraxetan were consistent with those from prior clinical trials. The rates of grade 3 or higher adverse effects (AEs) were 36% in the lutetium Lu 177 vipivotide tetraxetan arm vs 48% in the control arm. The respective rates of grade 5 AEs were 2% (n = 4) in the lutetium Lu 177 vipivotide tetraxetan arm vs 2% (n = 5) in the control arm; no grade 5 AEs were deemed treatment related in the lutetium Lu 177 vipivotide tetraxetan group; 1 patient experienced a treatment-related grade 5 AE in the control group.

"This [expanded approval] reflects the power of scientific innovation in advancing therapies that improve survival while prioritizing quality of life," Garcia added. "More importantly, it highlights the vast potential of radioligand therapies across oncology, opening new avenues for discovery and reaffirming our commitment to a future where cancer care is increasingly patient-centered, technology-driven, and personalized to meet the unique needs of every individual."

References

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
2. FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. March 28, 2025. Accessed March 28, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-radioligand-therapy-pluvicto-earlier-use-chemotherapy-psma-positive-metastatic-castration-resistant-prostate-cancer
3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer?utm_medium=email&utm_source=govdelivery
4. Morris MJ, Castellano D, Herrmann K, et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024;404(10459):1227-1239. doi:10.1016/S0140-6736(24)01653-2