A phase 1b, two-arm study of tolododekin alfa (ANK-101) in combination with an anti–PD-1/PD-L1 antibody in participants with advanced non–small cell lung cancer (NSCLC).

Abstract

TPS2678 Background: Tolododekin alfa (ANK-101) is an anchored immunotherapy linking IL-12 to aluminum hydroxide through an alum-binding protein (ABP). Direct delivery to tumors results in prolonged IL-12 local retention and limited systemic absorption. A Phase 1 study in advanced solid tumors demonstrated ANK-101 was well tolerated with evidence of antitumor activity, recruitment of CD8+ T cells, and induction of local programmed cell death ligand 1 (PD-L1) expression. ANK-101 is now being evaluated in combination with PD-1/PD-L1 checkpoint blockade (ICB) in patients with non-small cell lung cancer (NSCLC). Methods: This study is a Phase 1b, two-arm, open-label study of direct injection (IT) of tolododekin alfa administered in combination with an anti-PD-1/PD-L1 antibody in participants with locally advanced or metastatic NSCLC. Cohort A will be conducted in participants who have progressed on prior standard of care treatment with ICB and platinum-based chemotherapy, either in combination or sequentially. Cohort B will enroll participants with untreated locally advanced or metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 50%. Participants with targetable EGFR mutations or ALK rearrangements are excluded. In Cohort A, participants will receive tolododekin alfa at 250 µg/mL IT in combination with cetrelimab (anti-PD-1) intravenously (IV) Q3W at a dose of 360 mg for up to 8 cycles, followed by cetrelimab monotherapy for up to one year, unless they have unacceptable toxicity, clinical deterioration, confirmed tumor progression, or have withdrawn consent. In Cohort B, participants will receive tolododekin alfa at 250 µg/mL IT in combination with investigator’s choice of an FDA-approved ICB for first-line use as monotherapy in patients with TPS ≥" role="presentation" tabindex="0">≥ 50% IV Q3W at the approved dose for up to 8 cycles, followed by continued ICB according to the FDA-approved label. The primary objective is objective response rate by RECIST 1.1. Secondary endpoints include safety, duration of response, disease control rate, progression-free survival, and overall survival. In addition, lesion-level responses, serum PK analyses, and anti-drug antibody (ADA) levels will be assessed. Exploratory endpoints include measurements of selected serum cytokine levels and characterization of the composition of the tumor microenvironment before and on-treatment. This clinical trial is in progress. Clinical trial information: NCT07027514 .