STORM Therapeutics Initiates First-in-Class RNA Modification Therapy Combination Trial with Checkpoint Inhibitor
核心洞察
STORM Therapeutics (搜索) has dosed the first patient in a Phase 1b/2 combination study evaluating STC-15, a METTL3 (搜索) inhibitor, with LOQTORZI (toripalimab) for multiple cancer types.
The trial will enroll up to 188 patients with NSCLC, head and neck squamous cell carcinoma, melanoma, and endometrial cancer in the United States.
Previous Phase 1 data showed STC-15 achieved a 9% overall response rate and 67% disease control rate in patients with advanced malignancies.
STORM Therapeutics (搜索) has initiated dosing of the first patient in a Phase 1b/2 clinical collaboration with Coherus BioSciences, marking a significant milestone for the first RNA modifying enzyme inhibitor to enter combination therapy development. The study evaluates STC-15, a first-in-class METTL3 (搜索) inhibitor, in combination with LOQTORZI (toripalimab-tpzi), an anti-PD-1 (搜索) antibody, for treating non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, and endometrial cancer.
Novel Approach to Cancer Treatment Through RNA Modifications
STC-15 represents a breakthrough in cellular reprogramming through RNA modifications, targeting the METTL3 (搜索) enzyme to reprogram cancer cells. The combination strategy builds on clinical evidence showing STC-15 can achieve durable responses in patients who are refractory to immune checkpoint inhibitors, potentially enhancing the efficacy of PD-1 (搜索) blockade through complementary mechanisms.
Jerry McMahon, Chief Executive Officer of STORM Therapeutics (搜索), stated: "We are excited that the first patient is receiving treatment on our collaborative clinical study, evaluating the potential of STC-15 to enhance responses to immune checkpoint inhibitors. Our clinical data has demonstrated that STC-15 can achieve durable responses for patients who are refractory to immune checkpoint inhibitors, therefore combining it with LOQTORZI may further validate our hypothesis of treating cancer through cellular reprogramming and RNA modifications."
Study Design and Patient Population
The Phase 1b portion will conduct dose escalation to determine the safety profile of the combination and establish the recommended dose for STC-15. Following successful dose optimization, the Phase 2 expansion will evaluate efficacy across four distinct cancer types in up to 188 patients across the United States.
The trial design reflects the promising safety profile established in earlier studies. Final clinical results from a Phase 1 study of STC-15 in patients with advanced malignancies demonstrated the therapy is well tolerated and achieved tumor regressions at all dose levels evaluated, with an overall response rate of 9% and disease control rate of 67%. Pharmacokinetic simulations and safety data support advancing STC-15 into combination studies with checkpoint inhibitors.
Strategic Leadership Appointment
Concurrent with the trial initiation, STORM Therapeutics (搜索) appointed Atif Abbas, M.D. as Chief Medical Officer to lead the clinical development strategy. Dr. Abbas brings two decades of immuno-oncology drug development experience, encompassing IND to NDA/BLA submissions, product launches, and life cycle management. He received his medical degree from King Edward Medical University in Pakistan, with additional postdoctoral training at Yale University and Harvard Medical School, and has held roles of increasing responsibility at Merck KGaA, Abbvie, Astellas, Boehringer Ingelheim, and most recently as VP at Servier Pharmaceuticals.
Collaboration Structure
Under the clinical trial collaboration and supply agreement, Coherus will provide LOQTORZI to STORM, which serves as the sponsor of the Phase 1b/2 clinical combination trial. Both companies retain all commercial rights to their respective compounds, including as monotherapies or combination therapies, providing flexibility for future development strategies.
The collaboration leverages STORM's pioneering work in RNA modifying enzymes (RME) and world-leading understanding of cellular reprogramming through RNA biology. STC-15 is currently the first RNA modifying enzyme inhibitor to enter human clinical development, representing a novel therapeutic approach for cancer, inflammation, viruses, and CNS diseases.