Roche Presents Exploratory Phase III IMvigor010 Data Showing Benefit of Tecentriq in ctDNA-Positive Muscle-Invasive Urothelial Cancer at ESMO IO 2020

Compiled by Keke

On December 11, Roche presented an exploratory analysis of the Phase 3 clinical study IMvigor010 at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Virtual Congress. IMvigor010 is a global, Phase 3, open-label, randomized, controlled study evaluating the efficacy and safety of Tecentriq® (atezolizumab) as adjuvant monotherapy compared with clinical observation in patients with muscle-invasive urothelial carcinoma (MIUC) following surgery. The study enrolled 809 patients with MIUC who were at high risk of recurrence after resection. The primary endpoint, assessed by investigators, was disease-free survival (DFS), defined as the time from randomization to recurrence of MIUC or death.

Data from IMvigor010 showed that in patients with circulating tumor DNA (ctDNA), those treated with Tecentriq had improved disease-free survival (DFS) compared to clinical observation (median 5.9 months vs. 4.4 months; hazard ratio [HR] = 0.58; 95% CI: 0.43–0.79). Interim analysis of overall survival (OS) also demonstrated greater benefit with Tecentriq treatment in the ctDNA-positive population, with a median OS of 25.8 months in the Tecentriq group versus 15.8 months in the observation group (HR = 0.59; 95% CI: 0.41–0.86).

The primary efficacy outcomes of the exploratory analysis are as follows:

Roche noted that although these prespecified analyses were exploratory and could not be formally tested according to the statistical plan of the IMvigor010 study, these data further deepen the understanding of the disease and will provide a basis for new phase 3 studies in patients with ctDNA-positive muscle-invasive bladder cancer.

As presented at the American Society of Clinical Oncology 2020 (ASCO 20) Virtual Congress, in the intention-to-treat population, the IMvigor010 study did not meet its primary endpoint of disease-free survival (DFS) compared with observation in patients with high-risk muscle-invasive urothelial carcinoma (MIUC) (19.4 months in the Tecentriq group vs. 16.6 months in the observation group [HR=0.89; 95% CI: 0.74–1.08; p=0.2446]). In the interim analysis of overall survival (OS), the median was not reached in either treatment group (HR=0.85). Furthermore, the safety profile of Tecentriq was consistent with the known safety profile of monotherapy, and no new safety concerns were identified.

According to statistics, urothelial carcinoma accounts for approximately 90–95% of all bladder cancer cases. Muscle-invasive urothelial carcinoma (MIUC) is a type of urothelial carcinoma that has invaded the muscular layers of the bladder, ureter, or renal pelvis. Approximately 25% of newly diagnosed bladder cancer cases are identified as muscle-invasive disease, which carries a poorer prognosis compared to non-muscle-invasive urothelial carcinoma (non-MIUC). The current treatment goal for patients with MIUC is to provide early intervention to reduce the risk of disease recurrence or metastasis to other parts of the body.

As tumors grow, dying cells are replaced by new ones, releasing tumor DNA into the bloodstream. This DNA, known as circulating tumor DNA (ctDNA), can be utilized in various ways, including identifying patients with minimal residual disease who may benefit most from adjuvant therapy, as well as those who do not derive benefit from such treatment. In muscle-invasive urothelial carcinoma (MIUC), ctDNA serves as a strong prognostic marker for disease recurrence. Additional therapeutic options are needed after surgery, as approximately half of MIUC patients experience recurrence within two years post-surgery. Furthermore, given the absence of predictive or prognostic biomarkers in current clinical practice for MIUC, there is a pressing need for more personalized treatment approaches for this disease.

Dr. Levi Garraway, Chief Medical Officer and Global Head of Product Development at Roche, stated that by leveraging ctDNA and other biomarkers, they aim to gain deeper insights to enable more personalized treatment approaches. Bladder cancer is a complex and often difficult-to-treat disease; however, with a growing understanding of its biological characteristics, new therapeutic pathways are becoming increasingly clear.

As a cancer immunotherapy, Tecentriq may serve as a foundational combination agent with other immunotherapies, targeted drugs, and various chemotherapy regimens for a wide range of cancers. Currently, the drug has been approved in the United States, the European Union, and countries worldwide, either as monotherapy or in combination with targeted therapy and/or chemotherapy, for the treatment of non-small cell lung cancer, small cell lung cancer, certain types of metastatic urothelial carcinoma, melanoma, PD-L1-positive metastatic triple-negative breast cancer, and hepatocellular carcinoma.

Reference: Roche presents exploratory data from the Phase III IMvigor010 study in early bladder cancer at the ESMO Immuno-Oncology Virtual Congress 2020