Asher Biotherapeutics and Amgen are joining forces to evaluate a novel combination therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The collaboration will focus on assessing the safety and early efficacy of Asher Bio's etakafusp alfa, a CD8+ T cell targeted interleukin-2 (IL-2) immunotherapy, in conjunction with Amgen's IMDELLTRA® (tarlatamab), a DLL3-targeting Bispecific T-cell Engager (BiTE®) therapy. This Phase 1b study aims to address the significant unmet need in ES-SCLC treatment, where current options provide limited survival benefits.
Rationale for Combination Therapy
The rationale behind this collaboration lies in the potential of etakafusp alfa to enhance the effectiveness of T cell engagers like IMDELLTRA®. Etakafusp alfa is designed to selectively expand the CD8+ T cell population, which are crucial for anti-tumor activity. By improving effector function, tumor infiltration, and reversing T cell desensitization induced by T cell engagers, etakafusp alfa may synergize with IMDELLTRA® to improve patient outcomes.
"This clinical trial collaboration and supply agreement with Amgen allows us to further expand on the Phase 1 results for etakafusp alfa in a new combination with IMDELLTRA® in a global Phase 1b study in ES-SCLC," said Don O’Sullivan, Ph.D., Chief Business Officer of Asher Bio.
Study Design and Collaboration Details
Under the terms of the agreement, Amgen will sponsor and operationalize the global Phase 1b study. Asher Bio will retain full ownership of etakafusp alfa and will supply the drug to Amgen at no cost. The study will primarily focus on evaluating the safety and early efficacy of the combination in ES-SCLC patients.
Addressing Unmet Needs in SCLC
Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis, particularly in the extensive-stage. ES-SCLC is associated with a 3% five-year relative survival rate. The median survival following initial therapy is approximately 12 months. While initial response rates to first-line platinum-based chemotherapy are high, most patients relapse within months, necessitating further treatment options. Second-line treatments offer a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months). Third-line treatments, primarily chemotherapy, yield even shorter durations of response (median DoR: 2.6 months) and overall survival (median OS: 4.4-5.3 months).
Etakafusp Alfa: A Targeted Immunotherapy
Etakafusp alfa (AB248) is a novel CD8+ T cell selective IL-2 immunotherapy. It is engineered to selectively and potently activate CD8+ T-cells, the immune cells responsible for anti-tumor efficacy, while avoiding natural killer (NK) cells and regulatory T (Treg) cells. Asher Bio is currently evaluating etakafusp alfa in a Phase 1a/1b clinical trial (AB248-101) as a monotherapy and in combination with pembrolizumab in patients with advanced/metastatic solid tumors who have failed prior therapies. Early data from this trial demonstrate potent and selective CD8+ T cell activation, with initial evidence of anti-tumor activity and a generally well-tolerated safety profile.
