Regulatory Decision Summary for Jemperli

The purpose of this Supplement to a New Drug Submission (SNDS) is to seek marketing authorization for Jemperli in combination with platinum-containing chemotherapy for the treatment of adult patients with primary advanced or recurrent mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer.

After evaluation of the submitted data package, Health Canada authorized Jemperli for the following indication: Jemperli (dostarlimab for injection) is indicated in combination with carboplatin and paclitaxel for the treatment of adult patients with primary advanced or recurrent mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer who are candidates for systemic therapy.

This was a submission for a new indication. Please see Jemperli Product Monograph regarding the previously authorized indication.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

The submission was reviewed under Project Orbis.

Authorization was based on a Phase 3 multicentre, randomized, double-blind, placebo-controlled clinical study, RUBY Part 1, in adult patients with primary advanced (Stage III-IV) or recurrent endometrial cancer (EC).

The efficacy and safety results supporting the authorization were from a pre-planned subgroup analysis in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC.

In the dMMR/MSI-H subpopulation, patients were randomized 1:1 to receive either Jemperli 500 mg plus carboplatin AUC 5 mg/mL/min and paclitaxel 175 mg/m² every 3 weeks for 6 cycles followed by Jemperli 1,000 mg every 6 weeks (n = 60) or placebo plus carboplatin AUC 5 mg/mL/min and paclitaxel 175 mg/m² every 3 weeks for 6 cycles followed by placebo every 6 weeks (n = 62).

The study met its primary efficacy endpoint and demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in the Jemperli plus carboplatin and paclitaxel group. The median PFS was 30.3 months in the Jemperli plus carboplatin and paclitaxel group and 7.7 months in the placebo plus carboplatin and paclitaxel group. The hazard ratio was 0.29 (95% CI 0.172, 0.497, p<0.0001), corresponding to a 71% reduction in the risk of disease progression or death in patients receiving Jemperli plus carboplatin and paclitaxel.

In the dMMR/MSI-H subpopulation, the most common adverse reactions (≥10%) in the Jemperli plus carboplatin and paclitaxel arm were rash (40.4%), diarrhea (40%), hypothyroidism (23.1%), hypertension (21%), pyrexia (13.5%), alanine aminotransferase increased (11.5%) and dry skin (11.5%). Serious adverse reactions occurred in 13% of patients receiving Jemperli in combination with carboplatin and paclitaxel; the most common serious adverse reaction was sepsis, including urosepsis (6%). Fatal adverse reactions occurred in 6% of patients receiving Jemperli, including septic shock (3.8%) and myelosuppression (1.9%). Key safety findings are adequately described in the final Product Monograph (PM).

Overall, based on the evidence reviewed, the anticipated benefit outweighs the potential risks for Jemperli in combination with carboplatin and paclitaxel for the treatment of adult patients with primary advanced or recurrent dMMR/MSI-H EC who are candidates for systemic therapy.

The recommended dosage of Jemperli as combination therapy is 500 mg Jemperli administered as an intravenous infusion over 30 minutes every 3 weeks for 6 doses followed by 1,000 mg every 6 weeks for all cycles thereafter. Administration of Jemperli should continue according to the recommended dose and schedule until disease progression or, unacceptable toxicity, or up to 3 years.

Health Canada granted this submission priority review status.

For further details about Jemperli, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.

An updated Risk Management Plan (RMP) for Jemperli was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.