Pluvicto Receives Support for European Approval in PSMA-Positive mCRPC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Lutetium 177 (177Lu) vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617) in combination with androgen deprivation therapy (ADT) with or without androgen receptor (AR) pathway inhibition, for the treatment of adult patients with progressive prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with AR pathway inhibition and taxane-based chemotherapy.¹

The positive opinion was based on findings from the phase 3 VISION trial (NCT03511664), which showed that 177Lu–vipivotide tetraxetan plus best standard of care (SOC) significantly improved overall survival (OS) vs best SOC alone in patients with PSMA-positive mCRPC previously treated with AR pathway inhibition and taxane-based chemotherapy. Patients treated with 177Lu–vipivotide tetraxetan (n = 385) achieved a median OS of 15.3 months compared with 11.3 months for best SOC alone (n = 196; HR, 0.62; 95% CI, 0.52-0.74; P < .001).²

“People at this advanced stage of disease have already received many different treatments and have few alternatives left,” Karim Fizazi, MD, PhD, VISION trial investigator and head of Medical Oncology at Gustave Roussy in Villejuif, France, stated in a press release. “If approved in Europe, [177Lu–vipivotide tetraxetan] would represent a new type of precision medicine targeting a biomarker broadly expressed in [patients with] prostate cancer and provide a therapeutic option with demonstrated potential to improve outcomes. As a clinician this gives me hope for patients facing a very difficult situation.”

In March 2022, the FDA approved 177Lu–vipivotide tetraxetan for the treatment of adult patients with PSMA-positive mCRPC who have previously received AR pathway inhibition and taxane-based chemotherapy.³ The approval was also based on findings from the VISION trial.

VISION enrolled patients with CRPC who had at least 1 metastatic lesion and progressed following prior treatment with 1 or more approved AR pathway inhibitors and 1 or 2 taxane regimens.² Patients also needed to have at least 1 PSMA-positive metastatic lesion and no PSMA-negative lesions that would be excluded according to the protocol criteria. Patients were also required to have an ECOG performance status between 0 and 2, a life expectancy of at least 6 months, and adequate bone marrow and organ function.

Enrolled patients were randomly assigned 2:1 to receive 7.4 GBq (200 mCi) of 177Lu–vipivotide tetraxetan once every 6 weeks for 4 cycles plus best SOC, or best SOC alone. If patients in the experimental arm had evidence of response, they were permitted to receive 2 additional cycles of the radioligand therapy, per investigator discretion.

SOC excluded chemotherapy, immunotherapy, radium-223, and investigational drugs. Treatment continued until disease progression, unacceptable toxicity, lack of clinical benefit, or the need for treatment with a prohibited SOC agent.

Primary end points of the trial included radiographic progression-free survival (rPFS) and OS. Key secondary end points were comprised of objective response rate, disease control rate, time to first symptomatic skeletal event, safety, health-related quality of life, pain, and biomarker outcomes.

Additional data showed that at a median follow-up of 20.9 months, the median rPFS in the experimental arm was 8.7 months vs 3.4 months for SOC alone (HR, 0.40; 99.2% CI, 0.29-0.57; P < .001).

The median time to first symptomatic skeletal event or death for patients in the 177Lu–vipivotide tetraxetan arm was 11.5 months compared with 6.8 months in those on the SOC arm (HR, 0.50; 95% CI, 0.40-0.62; P < .001).

Among patients with measurable target lesions per RECIST v1.1 criteria, 9.2% of those in the investigative arm (n = 184) experienced a complete response compared with 0% of those in the control arm (n = 64). Partial responses were reported in 41.8% and 3.0% of those on the investigative and control arms, respectively.

Regarding safety, the most common any-grade adverse effects in the investigative arm included fatigue (43.1%), dry mouth (38.8%), nausea (35.3%), anemia (31.8%), back pain (23.4%), arthralgia (22.3%), decreased appetite (21.2%), and constipation (20.2%).

“This positive CHMP opinion for [177Lu–vipivotide tetraxetan] is an important step forward in our goal of bringing transformative innovation to more patients around the world,” Marie-France Tschudin, president, Innovative Medicines International & Chief Commercial Officer at Novartis, stated in a press release. “If approved by the European Commission, [177Lu–vipivotide tetraxetan] would be the first and only commercial radioligand therapy for people with advanced prostate cancer in Europe. We are committed to exploring the potential of radioligand therapy to address unmet needs in prostate cancer, including in earlier stages of disease.”

References

1. Novartis receives positive CHMP opinion for Pluvicto® for patients with progressive, PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. October 14, 2022. Accessed October 14, 2022. https://bit.ly/3Td7jDA
2. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA. March 23, 2022. Accessed October 14, 2022. https://bit.ly/3LaWA8w