Ankyra Therapeutics Initiates Phase 1b Trial of Anchored IL-12 Immunotherapy Combined with Checkpoint Blockade in Lung Cancer
核心洞察
Ankyra Therapeutics (搜索) has dosed the first patient in its Phase 1b LANTERN trial evaluating tolododekin alfa (搜索), an anchored IL-12 (搜索) drug conjugate, combined with anti-PD-1 (搜索)/PD-L1 (搜索) checkpoint blockade in non-small cell lung cancer patients.
The study will assess both first-line treatment in patients with tumor proportion scores ≥50% and second-line treatment in patients who progressed after initial therapy for metastatic, non-mutated NSCLC.
Previous Phase 1 monotherapy data published in Nature Communications demonstrated clinical activity with no dose-limiting toxicity in heavily pre-treated solid tumor patients.
Ankyra Therapeutics (搜索) has announced the dosing of the first patient in its Phase 1b clinical trial evaluating tolododekin alfa (搜索) (ANK-101), a first-in-class anchored IL-12 (搜索) immunotherapy, in combination with immune checkpoint blockade for the treatment of non-small cell lung cancer (NSCLC). The ANK-101-004 study (NCT07027514), also known as the LANTERN trial, represents a significant milestone for the Cambridge-based biotechnology company's novel anchored drug conjugate platform.
Study Design and Patient Population
The Phase 1b trial will evaluate tolododekin alfa (搜索) in combination with the anti-PD1 agent cetrelimab in two distinct patient cohorts. The first cohort includes patients who have progressed after initial treatment of metastatic, non-mutated NSCLC, while the second cohort will assess the combination as first-line treatment in patients with metastatic, non-mutated NSCLC and a tumor proportion score (TPS) of ≥50%.
"While there has been considerable progress in the treatment of lung cancer many patients do not respond to current approaches," said Thomas Marron, MD, PhD, Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai and Chief Medical Officer of OCCAM Immune (搜索), who serves as the principal investigator of the study. "The potential use of anchored IL-12 (搜索) to drive better responses without adding appreciable toxicity could be an important advance for patients."
Promising Monotherapy Results
The combination trial builds on encouraging Phase 1 monotherapy data recently published in Nature Communications. The initial study demonstrated clinical activity with no dose-limiting toxicity in heavily pre-treated patients with solid tumors. According to Howard L. Kaufman, MD, CEO at Ankyra Therapeutics (搜索), "Tolododekin alfa (搜索) has already demonstrated objective responses as a single agent in patients with anti-PD-1 (搜索)-refractory cancers in phase 1 trials."
The monotherapy study was conducted at several centers in the United States and Canada in patients with progressive solid tumors, with Part 1 focusing on patients with superficially accessible tumors. "Tolododekin alfa (搜索) demonstrated a tolerable safety profile and treatment was associated with monotherapy clinical activity in several types of cancers," Kaufman noted.
Innovative Anchored Drug Conjugate Technology
Tolododekin alfa (搜索) represents a novel approach to IL-12 (搜索) delivery, composed of interleukin-12 linked to aluminum hydroxide. This anchored drug conjugate technology enables local delivery of functional IL-12 to the tumor microenvironment, where it remains biologically active for several weeks with only transient exposure to systemic circulation. This design aims to avoid the systemic toxicity that has historically limited IL-12's therapeutic potential.
Joe Elassal, MD, chief medical officer at Ankyra Therapeutics (搜索), emphasized that "the emerging data supports the proposed mechanism of action for tolododekin alfa (搜索) and provides initial proof of concept for the anchored drug conjugate platform."
Collaborative Research Efforts
Ankyra is collaborating with OCCAM Immune (搜索) at Mount Sinai to support the LANTERN clinical trial. Through state-of-the-art immune profiling, OCCAM Immune aims to generate a comprehensive immune atlas to correlate immune modulation with therapeutic efficacy and disease progression, advance biomarker discovery, and deepen mechanistic insights into Ankyra's therapeutic approach.
Expanding Clinical Pipeline
The company has presented additional data at the Society for Immunotherapy of Cancer annual meeting, including biomarker analysis showing that baseline levels of circulating natural killer T (NKT) cells may serve as predictive biomarkers of response to anchored IL-12 (搜索) treatment. Ankyra is also developing ANK-201 (搜索), a next-generation candidate that expands the company's pipeline beyond cytokines.
The anchored drug conjugate platform has demonstrated versatility across species, with collaborative research including a canine anchored IL-12 (搜索) conjugate (JEN-101 (搜索)) being evaluated in dogs with melanoma through a partnership with the University of Illinois at Urbana-Champaign and Jenga Biosciences (搜索).