NEW YORK – Innovent Biologics recently garnered regulatory approval in China for its ROS1 inhibitor Dovbleron (taletrectinib) in patients with advanced ROS1-positive non-small cell lung cancer who've received prior ROS1 tyrosine kinase inhibitors (TKIs), and inked an exclusive deal with Roche to develop its investigational DLL3-targeted antibody-drug conjugate (ADC) in small cell lung cancer.
Dovbleron's approval was based on results from the Phase II TRUST-I trial, in which researchers evaluated Dovbleron in Chinese patients with ROS1-positive NSCLC, including those who had had prior ROS1 TKIs and ROS1 TKI-naïve individuals. In the ROS1 TKI-pretreated group, the objective response rate was 52 percent, and in the ROS1 TKI-naïve group, it was 91 percent.
"The treatment landscape for advanced ROS1-positive NSCLC remains challenging, especially for patients with brain metastases, who account for more than half of patients who have progressed following initial treatment with a ROS1 TKI, as well as those patients who develop resistance mutations," Caicun Zhou, director of the department of oncology at Shanghai East Hospital at Tongji University, said in a statement, adding that the drug showed "significant therapeutic effects on brain lesions" and was effective in patients who had become resistant to Pfizer's first-generation ROS1 inhibitor Xalkori (crizotinib).
Innovent has submitted a second new drug application (NDA) to China's National Medical Products Administration (NMPA) seeking approval for Dovbleron as a treatment for ROS1-positive advanced NSCLC patients who are ROS1 TKI-naïve. The NMPA is evaluating that application under priority review.
Shortly after Dovbleron's approval in China, Innovent's partner Nuvation Bio submitted an NDA to the US Food and Drug Administration seeking its approval in both ROS1 TKI-naïve and -pretreated advanced ROS1-positive NSCLC patients. The FDA is expected to make a decision on the application by June 23, 2025.
Innovent also this week announced a collaboration and exclusive license agreement with Roche to develop its DLL3-targeted drug IBI3009 in SCLC. Under the agreement, Roche will gain exclusive global rights to develop, manufacture, and commercialize the ADC. The two companies will collaborate on early-stage development of the candidate, then Roche will take over full development responsibilities. Innovent will receive an upfront payment of $80 million and is eligible to receive up to $1 billion in development and commercial milestone payments, along with tiered royalties on net sales.
Regulators in Australia, China, and the US have already cleared investigational new drug (IND) applications, allowing sponsors to begin clinically testing IBI3009 in those regions. A Phase I study in SCLC and neuroendocrine tumors has already started in Australia.
Drugmakers have taken different approaches to selecting patients for clinical trials of DLL3-targeted drugs since the biomarker is overexpressed in many tumors, including around 80 percent of SCLC and neuroendocrine tumors, but is not typically expressed on normal cells. It is not immediately clear if researchers will gauge the impact of DLL3 expression on patients' ability to respond to IBI3009 in these clinical trials.