Regulatory Decision Summary for LARTRUVO

The clinical efficacy and safety assessment of LARTRUVO was based on the results of a Phase II study known as JGDG. In this clinical trial, a total 133 soft tissue sarcoma patients whose disease was not amenable to curative treatment with radiotherapy or surgery were randomized 1:1 to treatment with LARTRUVO plus doxorubicin (the Investigational Arm, n = 66) or to doxorubicin alone (the Control arm, n = 67), respectively. The Safety population consisted of 64 and 65 patients, respectively (two patients in each arm did not receive study therapy). The key endpoint for this study was overall survival (OS).

The combination of LARTRUVO and doxorubicin gave rise to a statistically significant 11.8 month improvement in OS compared to doxorubicin alone, which corresponded to a 48% reduction in the risk of death (unstratified Hz ratio = 0.52 [95% CI: 0.34, 0.79]; p = 0.0017). The median OS was 26.5 months in the Investigational Arm compared to only 14.7 months in the Control Arm. These results, while promising, were not considered substantial evidence of efficacy for the LARTRUVO combination therapy over a standard of care since there were small numbers of patients enrolled in the Phase II JGDG study and they represented a heterogeneous group where imbalances in overall tumour burden and STS sub-types (with possibly varying degrees of aggressive behaviours) between the two arms may have contributed to the overall outcomes of the study results.

With respect to safety, patients treated with the combination of LARTRUVO and doxorubicin experienced more neutropenia, musculoskeletal events and infusion-related reactions compared to patients treated with doxorubicin alone. The most serious adverse reactions were infusion-related events. Four patients experienced serious hypersensitivity/ anaphylaxis reactions in the Phase II JGDG study within 10 minutes after the start of the first LARTRUVO infusion and required immediate attention including prolonged hospitalization with one case resulting in death. A Risk Management Plan was submitted and reviewed for these and other adverse reactions. The Product Monograph includes a Serious Warnings and Precautions for serious infusion-related reactions and is considered the primary source of risk mitigation measures for LARTRUVO.

The results of the Phase II JGDG study support promising evidence of efficacy with an acceptable safety profile for LARTRUVO when used in combination with doxorubicin for the treatment of adult patients with advanced soft tissue sarcoma whose disease is not amenable to curative treatment with radiotherapy or surgery and for whom treatment with an anthracycline-containing regimen is appropriate. A Phase III trial (Study JGDJ) is underway to confirm the benefit of the LARTRUVO and doxorubicin combination therapy in these patients.

A Notice of Compliance was issued under the Notice of Compliance with Conditions (NOC/c) policy.

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