Regulatory Decision Summary for Polivy

Conditional authorization was primarily based on the results from an international, multicenter, open-label, phase 1b/2 study in patients with relapsed or refractory diffuse large B-cell lymphoma. In the phase 2 study period, a randomized cohort of 80 patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, who are not eligible for autologous stem cell transplant and have received at least one prior therapy were enrolled. Patients received either Polivy plus bendamustine and rituximab (pola+BR arm, n = 40) or bendamustine and rituximab alone (BR arm, n = 40).

The primary objective of the randomized patient cohort was to compare the complete response (CR) rates between patients treated with Polivy in combination with bendamustine (B) and rituximab (R) versus BR alone. The CR rate for patients in the pola+BR arm was 40% versus 17.5% for patients in the BR arm. This was supported by secondary endpoints, including objective response rate, best overall response rate and duration of response.

The most common adverse reactions (AR) reported in clinical trials with Polivy included neutropenia, thrombocytopenia, and anemia. Other commonly reported ARs (>10%) included diarrhoea, abdominal pain, fatigue, pyrexia, pneumonia, weight decreased, decreased appetite, hypokalemia, hypoalbuminemia, hypocalcaemia, peripheral neuropathy, dizziness, cough and pruritis. Patients treated with Polivy also experienced higher incidences of infusion-related reactions, hepatic toxicity, gastrointestinal toxicity, arthralgia and skeletal pain. Overall, patients treated with pola+BR experienced more Grade ≥3 AEs (84.4% versus 74.4%), attributed to higher incidences of neutropenia, thrombocytopenia, anemia, lymphopenia, pancytopenia and pneumonia. Neutropenia and thrombocytopenia were the most common reasons for treatment discontinuation. Four fatal infections occurred in each treatment group. The risks associated with polatuzmab vedotin are considered tolerable and manageable, and have been adequately described in a Serious Warnings and Precautions Box, Warnings and Precautions and Adverse Reactions sections of the product monograph.

Given the study design, there is residual uncertainty regarding the magnitude of the treatment effect with the addition of Polivy to BR. Nevertheless, the observed treatment benefit, in the context of a conditional authorization, demonstrated promising clinical evidence in terms of response rates and duration of response in patients with r/r DLBCL which shows a promising benefit/risk profile for the proposed patient population. As a condition of authorization, the sponsor will be required to commit to file phase 3 trial data to confirm the efficacy of Polivy and the benefit/risk balance in patients with DLBCL.

The recommended dose of Polivy is 1.8 mg/kg.