Regulatory Decision Summary for Tecentriq / Tecentriq SC

The purpose of this submission was as follows:

• To seek market authorisation for a new formulation of atezolizumab intended for administration using the subcutaneous (SC) route in the following authorised indications: 1L Extensive-Stage Small Cell Lung Cancer (ES-SCLC), 1L Non-Small Cell Lung Cancer (NSCLC) and 1L Hepatocellular Carcinoma (HCC) and Locally Advanced or Metastatic Triple-Negative Breast Cancer (TNBC).

• To include additional dosage regimens of Tecentriq (IV formulation) for the authorised TNBC indication.

Tecentriq (an intravenous formulation of atezolizumab), alone or in combination with chemotherapy, is authorised in Canada for the treatment of first line (1L) Extensive-Stage Small Cell Lung Cancer (ES-SCLC), Non-Small Cell Lung Cancer (NSCLC), 1L Hepatocellular Carcinoma (HCC) and Locally Advanced or Metastatic Triple-Negative Breast Cancer (TNBC). The current submission provides data to support a new subcutaneous (SC) formulation of atezolizumab, namely, Tecentriq SC, to be administered at 1,875 mg every 3 weeks in the thigh for the same authorised indications of intravenous Tecentriq. Authorization was supported by one clinical study: BP40657 (hereinafter IMscin001).

IMscin001 was a comparative study of Tecentriq SC and Tecentriq in patients with previously treated locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who are cancer immunotherapy (CIT)-naive and for whom prior platinum therapy has failed. IMscin001 demonstrated that the exposure to atezolizumab resulting from Tecentriq SC (1875 mg every 3 weeks in the thigh) is not unacceptably less than that achieved with the standard atezolizumab intravenous (IV) dose from Tecentriq.

In terms of risk, the overall proportion of patients having adverse events was similar between treatment arms; however, injection site reactions (ISR) were identified as new adverse events associated with Tecentriq SC and mainly resulted in injection site pain and injection site reaction. In the Tecentriq SC arm, following a median follow up of 4 months, 2 fatal adverse events which were considered by the Investigator as treatment-related (pneumonia aspiration and toxic epidermal necrolysis) were reported with Tecentriq SC versus none being reported with Tecentriq arm. However, following an additional 2 months follow up (i.e., a median of 6 months follow up), no additional treatment related deaths were reported. Overall, the safety findings did not raise new safety concerns and were consistent with the previous observations for Tecentriq.

The exposure to atezolizumab resulting from Tecentriq SC is not less than that achieved with the standard atezolizumab IV dose. The level of efficacy as well as the safety profile of Tecentriq SC is therefore not expected to be appreciably different to that of Tecentriq. Accordingly, Tecentriq SC is considered to have a benefit-risk profile that is comparable to that of the currently authorized Tecentriq for the authorised indications.

The current submission additionally seeks the inclusion of the dosage regimens 1,200-mg q3w and 1,680-mg q4w of Tecentriq (IV formulation) to the authorised TNBC indication. The flexible dosage regimens 840-mg q2w or 1,200-mg q3w or 1,680-mg q4w have been already authorised for all the other Tecentriq indications in Canada. The authorization of the 1,200-mg q3w and 1,680-mg q4w dose regimens of Tecentriq (IV formulation) in the TNBC indication is supported by a demonstration that exposure to atezolizumab resulting from intravenous Tecentriq is comparable across the authorised dosage regimens and as a result, comparable efficacy and safety are expected to be maintained across the alternative dosage regimens in all the authorised indications, including the TNBC indication.

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

The chemistry and manufacturing information submitted for Tecentriq / Tecentriq SC 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-harm-uncertainty profile was favourable for Tecentriq (1,200 mg/20 mL) / Tecentriq SC (840 mg/14 mL) for the approved indication 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 Tecentriq / Tecentriq SC, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.