IMspire150 Study Meets Primary Endpoint of PFS in Patients With Melanoma

The combination of atezolizumab (Tecentriq), cobimetinib (Cotellic), and vemurafenib (Zelboraf) reduced the risk of disease progression or death compared with placebo in patients withBRAFV600 mutation—positive advanced melanoma, meeting the primary endpoint of progression-free survival (PFS) in the phase III IMspire150 study (NCT02908672), according to a press release from Roche.¹

The PFS demonstrated in the study was considered to be significant and clinically meaningful. The data were not reported, however, Roche plans to present the results from IMspire150 at an upcoming conference and discuss the positive data with the FDA and the European Medicines Agency (EMA).

“By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced,BRAF-mutant melanoma," said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche. "We look forward to discussing the results with health authorities around the world.”

The double-blind, placebo-controlled, randomized trial divided patients into 2 arms. In the experimental arm, participants were given intravenous atezolizumab 840 mg plus cobimetinib 60 mg tablets plus vemurafenib 720 mg tablets plus 1 tablet of vemurafenib placebo. Patients in the second arm of the study will receive intravenous atezolizumab placebo on days 1 and 15, as well as cobimetinib 60 mg tablets, and vemurafenib 960 mg tablets.²

All patients in the study are treated on days 1 through 28 of a 28-day cycle. Individuals will be kept on treatment incidences of disease progression, death, unacceptable toxicity, withdrawal of consent or pregnancy, which are determined by the study investigators.

The key secondary endpoints being explored in IMspire150 include PFS per independent review committee, the percentage of patients with an objective response, duration of response, overall survival, and the percentage of patients with adverse events.

Patients may enroll in the study if they have histological confirmation of metastatic or locally advanced melanoma. These individuals must be treatment naïve with documentedBRAFv600 mutation-positive disease, and Eastern Cooperative Group (ECOG) performance status of 0 or 1, measurable disease, and a life expectancy of at least 18 weeks.

The key exclusion criteria for the trial are related to the presence of other cancers, ocular issues, cardiac dysfunction, and the presence of central nervous system lesions of metastases. There is also an extensive list of other exclusion criteria.

IMspire150 is a collaborative effort between Genentech, Inc. developer of atezolizumab, Exelixis, the developer of cobimetinib, and Roche, the developer of vemurafenib.¹

A key drug in the IMspire150 combination, atezolizumab, already has FDA indications and has shown promise in other clinical trials across different malignancies. Specifically, the drug is approved for the treatment of non—small cell lung cancer, metastatic urothelial cancer, and PD-L1-positive metastatic triple-negative breast cancer, in the United States, the European Union, and in other countries.

The phase III IMspire150 study is ongoing with a target completion date of July 2023.

References

1. Roche announces positive Phase III study results for Tecentriq plus Cotellic and Zelboraf in people with previously untreated BRAF V600 mutation-positive advanced melanoma [press release]. Basel, Switzerland: Roche; December 13, 2019. https://bit.ly/2RNTyyE. Accessed December 13, 2019
2. A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma. ClinicalTrials.gov. https://bit.ly/2LS2IGG. Accessed December 13, 2019.