Regulatory Decision Summary for Loqtorzi

This New Drug Submission (NDS) was filed to obtain market authorization for Loqtorzi (toripalimab for injection) for the following indications:

• in combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC).

• as a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.

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

Nasopharyngeal carcinoma (NPC) is a rare disease in Canada, though higher rates are observed among individuals of Southeast Asian ancestry and in Inuit populations. For recurrent or metastatic NPC, platinum-based doublets (most commonly gemcitabine plus cisplatin) constitute the first-line standard of care; however, this combination is not curative and a significant unmet need exists for the development of additional treatment options for this patient population. Beyond this setting, there is no established standard therapy in Canada, and treatment options are limited to clinical trials or palliative chemotherapy.

Loqtorzi, a PD-1 targeting monoclonal antibody, was studied in patients with NPC in two clinical studies. In a Phase 3, randomized, double-blind, placebo-controlled trial, patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease were treated with Loqtorzi in combination with cisplatin and gemcitabine or with placebo plus cisplatin and gemcitabine. Treatment with Loqtorzi resulted in clinically meaningful and statistically significant improvements in both progression-free survival (Hazard Ratio [HR] = 0.52 [95% Confidence Interval {CI}: 0.359, 0.740]) and overall survival (HR = 0.63 [95% CI: 0.45, 0.89]) compared to placebo. The safety profile of Loqtorzi in combination with cisplatin and gemcitabine was consistent with the known and expected safety profiles of the individual components of the treatment regimen. Treatment with Loqtorzi can cause immune-mediated adverse reactions, which is consistent with the class of anti-PD-1 monoclonal antibodies. The risks of treatment with Loqtorzi can be mitigated and managed through labelling in the Product Monograph and through routine post-market pharmacovigilance activities. Thus, the use of Loqtorzi in combination with cisplatin and gemcitabine provides a clinical benefit over cisplatin and gemcitabine alone, with a manageable safety profile, and offers an additional first-line treatment option for patients with metastatic or recurrent, locally advanced NPC.

In the second study, Loqtorzi was evaluated as monotherapy in patients with recurrent or metastatic NPC who had progressed following platinum-based chemotherapy. This was a single-arm, Phase 2 trial. Treatment with Loqtorzi resulted in a notable objective response rate (ORR) of 21% (95% CI: 15.1, 27.8) and a meaningful median duration of response (DoR) of nearly 15 months. The safety profile observed in this study was consistent with that seen in the Phase 3 trial and with the known safety profile of anti-PD-1 monoclonal antibodies, with no new or unexpected safety concerns identified.

Although the single-arm design limits comparative interpretation, the observed magnitude and durability of response, together with an acceptable safety profile, support a positive benefit-risk assessment in this patient population. Given the absence of an established standard of care beyond first-line platinum-based chemotherapy, the results of this Phase 2 study, along with the clinical benefit demonstrated in the first-line Phase 3 trial, provide supportive evidence of Loqtorzi’s efficacy and safety as monotherapy in previously treated NPC.

The Canadian Risk Management Plan (RMP) for Loqtorzi was submitted to Health Canada as part of this NDS. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP is considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures for Loqtorzi. This includes providing information in the Product Monograph and identifying populations and areas where more data are needed. Results related to the safety and effectiveness of Loqtorzi from ongoing and planned studies will be submitted in Periodic Safety Update Reports (PSURs) as they become available.

The chemistry and manufacturing information submitted for Loqtorzi has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

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

Overall, the benefit-risk profile was considered favourable for Loqtorzi for the authorized indications when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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