Phase 2 KICKSTART Trial: Tomivosertib Plus Pembrolizumab in NSCLC Topline Results

eFFECTOR Therapeutics, a California-based company specializing in the development of selective translation regulator inhibitors (STRIs) for cancer treatment, has reported preliminary findings from the Phase 2 KICKSTART trial. The trial investigated the efficacy of tomivosertib, an STRI, when combined with pembrolizumab as a frontline therapy for non-small cell lung cancer (NSCLC) patients with a PD-L1 expression of 50% or higher.

The study's primary endpoint was progression-free survival (PFS), and the results indicated a hazard ratio of 0.62 in favor of tomivosertib, based on 36 events. However, the two-sided p-value for PFS was 0.21, which did not meet the pre-specified threshold of p≤0.2. The median PFS was 13.0 weeks for the tomivosertib and pembrolizumab combination and 11.7 weeks for the placebo and pembrolizumab combination. The overall survival data is not yet mature, and no clear advantage for tomivosertib was observed. Additionally, there were more Grade 3 or higher treatment-related adverse events in the tomivosertib group (67%) compared to the placebo group (37%).

Despite modest activity observed for tomivosertib, eFFECTOR's CEO, Steve Worland, stated that there is no clear path forward for its development in frontline NSCLC based on the current data. He expressed gratitude to all those involved in the trial and confirmed that the company will continue to analyze the data with the hope of presenting findings at a future medical conference.

Worland also highlighted the company's ongoing focus on advancing another drug candidate, zotatifin, which targets a different mechanism from tomivosertib. Zotatifin is set to enter a potentially pivotal trial for estrogen receptor positive (ER+) breast cancer later this year. The company's strategy remains to efficiently advance zotatifin's development, following positive median PFS and safety data presented at the San Antonio Breast Cancer Symposium.

Furthermore, eFFECTOR plans to report additional data for zotatifin combined with fulvestrant and abemaciclib in the second half of 2024. Additionally, an investigator-sponsored trial of tomivosertib in acute myeloid leukemia (AML) will continue, as its potential to inhibit the production of survival proteins Mcl-1 and Bcl-2, which are crucial for leukemia cell survival, is distinct from its rationale in NSCLC.

eFFECTOR is a clinical-stage biopharmaceutical company that pioneers the development of STRIs, which target the eIF4F complex and its activating kinase, MNK. Their product candidates are designed to influence the expression of a network of proteins, including oncoproteins and immunosuppressive proteins in T cells, that control tumor growth, survival, and immune evasion. The company has a global collaboration with Pfizer to develop inhibitors targeting eIF4E.