Dr Rodriguez on Tolododekin Alfa in NSCLC

Tolododekin alfa (ANK-101) is a novel anchored immunotherapy that links interleukin-12 (IL-12) to aluminum hydroxide via an alum-binding protein. When injected directly into tumors, it achieves prolonged local IL-12 retention while minimizing systemic absorption. Early phase 1 data in advanced solid tumors showed the agent was well tolerated and demonstrated antitumor activity, including CD8+ T-cell recruitment and upregulation of PD-L1 expression within the tumor. These findings provided the rationale for combining ANK-101 with PD-1/PD-L1 immune checkpoint blockade (ICB) in non–small cell lung cancer (NSCLC).

The current study (NCT07027514) is a phase 1b, 2-arm, open-label trial evaluating intratumoral tolododekin alfa in combination with anti–PD-1/PD-L1 therapy in patients with locally advanced or metastatic NSCLC. Cohort A enrolls patients who have previously progressed on both ICB and platinum-based chemotherapy. These participants receive tolododekin alfa plus cetrelimab (anti–PD-1) every 3 weeks for up to 8 cycles, followed by cetrelimab monotherapy for up to 1 year. Cohort B targets treatment-naive patients with a PD-L1 tumor proportion score of 50% or greater, pairing tolododekin alfa with the investigator's choice of an FDA-approved first-line ICB. Patients with actionable EGFR mutations or ALK rearrangements are excluded from both cohorts.

The primary end point is objective response rate per RECIST 1.1. Secondary end points include safety, duration of response, disease control rate, progression-free survival, and overall survival. Pharmacokinetic analyses and antidrug antibody assessments are also planned. Exploratory end points will examine serum cytokine levels and tumor microenvironment composition at baseline and on-treatment, providing insight into the biological mechanisms underlying any observed clinical activity. The trial is currently enrolling.