Regulatory Decision Summary for Kimmtrak

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):


Therapeutic area:

Antineoplastic Agent

Type of submission:

New Drug Submission

Control number:

What was the purpose of this submission?


Uveal melanoma (UM) is a rare type of melanoma, which is biologically, clinically, and genetically distinct from skin melanoma. Unfortunately, UM is less sensitive to immune check point inhibitors and other current therapies. There has been no significant improvement in survival for patients with metastatic UM. This means that UM can be considered a life-threatening disease with no effective therapy available once the cancer has spread elsewhere in the body (metastatic UM).

The sponsor developed Tebentafusp (Kimmtrak) as a new treatment option, which works by redirecting the immune system to detect and destroy melanoma cancer cells. It has shown a significant survival benefit in the pivotal trial (IMCgp100-202). Tebentafusp is given intravenously in a hospital-like setting, so that patients can be monitored for 16 hours after administration. This is because most adverse reactions occur during the first three administrations and can be successfully treated.


Why was the decision issued?


Tebentafusp was assessed based on the results of the pivotal study IMCgp100. In this study, 378 adult patients with metastatic UM either received Tebentafusp or the current standard of care. Across both study groups, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity. The major efficacy outcome was overall survival (OS). Patients were between 23 years and 92 years of age, 87% were Caucasian and an equal portion of males and females. The median duration of follow up for all patients was 14.1 months. The study met its primary endpoint OS with a hazard ratio (HR) of 0.51, and a 95% confidence interval (CI) of (0.37, 0.71), and a p-value of 0.0001 (below the interim efficacy boundary of 0.006). This means that in the Tebentafusp group the risk of dying was reduced by 49% (ranging from 29% to 63%) when compared with the standard of care (investigator’s choice group). The OS estimates (median months) were 21.7 (95%CI of 18.6 to 28.6) for the Tebentafusp arm, and 16 months (95% CI of 9.7 to 18.4) for the investigator’s choice arm. This is considered clinically meaningful and significant.

The most common adverse reactions were cytokine release syndrome (CRS), skin reactions, fatigue, nausea, chills, abdominal pain, headache and vomiting. The most common laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, elevated liver functions, decreased hemoglobin, and decreased phosphate. There were no drug-related deaths. Only few patients exited the study due to drug-related adverse events (2.4% in the Tebentafusp and 2% in the investigator’s choice study group). Nonetheless, a serious warning and precaution section was added in the product monograph to inform about CRS, which can be serious or life-threatening, and provide risk mitigation information by monitoring for at least 16 hours following the first three infusions.

Metastatic UM is a serious/life-threatening disease with a poor prognosis based on existing therapies. The survival benefit identified in the Tebentafusp arm in combination with an appropriate risk management strategy (CRS, skin reaction, elevated liver enzyme management algorithm and dosing protocol) provide sufficient evidence for a positive benefit-risk profile in support of Tebentafusp.

For more information on Health Canadas decision, please view the Summary Basis of Decision.


Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.