Regulatory Decision Summary for Pluvicto

Authorization was primarily based on a multicentre, open-label, controlled pivotal phase 3 trial in adult patients with (PSMA)-positive metastatic castration-resistant prostate cancer who have received at least one androgen receptor pathway inhibitor and taxane-based chemotherapy. A total of 831 patients were enrolled to receive either Pluvicto 7.4 GBq (gigabecquerel) Q6W up to 6 cycles plus BSoC (Best Standard of Care) (N = 551) or BSoC alone (N = 280) until disease progression, or unacceptable toxicity. The alternative primary efficacy endpoints were overall survival (OS) and radiographic progression free survival (rPFS) assessed by blinded independent central review. At the date cutoff for the submission, the OS was 15.3 months for Pluvicto plus BSoC compared to 11.3 months for BSoC only. Interpretation of the magnitude of the rPFS effect was limited due to a high degree of censoring from early drop out in the control arm. In the context of the recommended condition of use and the available treatment options, these efficacy results are considered clinically significant.

The safety of Pluvicto was evaluated in 529 patients with progressive, PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who received at least one dose of randomized treatment. Patients received at least one dose of either Pluvicto 7.4 GBq (7,400 MBq, 200 mCi) administered every 6 to 10 weeks plus BSoC (N = 529) or BSoC alone (N = 205) until disease progression, or unacceptable toxicity. The most common adverse reactions (frequency ≥ 10%) occurring at a higher incidence in patients who received ¹⁷⁷Lu-PSMA-617 plus BSoC were anemia, leukopenia, lymphopenia, thrombocytopenia, abdominal pain, diarrhea, vomiting, weight loss, urinary tract infection, constipation, dry mouth, nausea, deceased appetite, and fatigue. Treatment-emergent serious adverse event (SAEs) ≥ 1% of patients were anemia, urinary tract infection, haematuria, sepsis, acute kidney injury, back pain, pneumonia, pyrexia, bone pain, pancytopenia, pulmonary embolism, spinal cord compression. Fatalities due to adverse events occurred in 3.6% of patients who received ¹⁷⁷Lu-PSMA-617 including two deaths due to fatal pancytopenia, two deaths due to intracranial hemorrhage and subdural hematoma, and five deaths due to sepsis. Fatalities due to adverse events occurred in 2.9% of patients who received BSoC alone, ¹⁷⁷Lu-PSMA-617 did not show an unexpectedly higher death rate compared to the control arm. The safety findings are adequately described in the final approved Product Monograph including the Patient Medication Information.

Based on mechanism of action for therapeutic radiation associated with ¹⁷⁷Lu-PSMA-617, Pluvicto is considered genotoxic/mutagenic as well as potentially carcinogenic.

Pluvicto represents a new treatment option for adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have received at least one androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. Based on the evidence reviewed, the benefit/risk profile is considered favorable for Pluvicto under the recommended condition of use.

The recommended dose of Pluvicto is 7.4 GBq given as a slow intravenous injection or infusion Q6W up to 6 cycles until disease progression or unacceptable toxicity.

For more information on Health Canada's decision, please view the Summary Basis of Decision.