Dose expansion data from iintune-1, a phase 1/2 study of the STING agonist dazostinag plus pembrolizumab as first-line (1L), in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (RM-SCCHN).

Abstract

6020 Background: Checkpoint inhibitors (CPIs) such as pembrolizumab (pembro) can lead to improved outcomes and durable responses in patients (pts) with RM-SCCHN. However, only a subset of pts with RM-SCCHN experience this benefit, and an unmet need for better treatments remains. STimulator of INterferon Genes (STING) agonism enhanced the response to CPIs preclinically. Dazostinag (dazo) is a small molecule STING agonist that has shown antitumor activity and activation of innate and adaptive immune responses in pts with solid tumors in the dose escalation part of iintune-1, with a recommended dose for expansion of 5 mg in combination with pembro. We report data from the ongoing dose expansion cohort 2A of iintune-1 in the first 30 pts with incurable 1L RM-SCCHN with a PD-L1 combined positive score (CPS) ≥1, treated with dazo in combination with pembro (NCT04420884). Methods: Pts receive dazo 5 mg IV on Days 1, 8, 15 plus pembro 200 mg IV on Day 1, in 21-day cycles. Primary endpoints are safety and tolerability. Secondary endpoints include investigator-assessed overall response rate (ORR) per RECIST 1.1 and duration of response (DOR). Dose optimization is planned as part of expansion. Results: As of Dec 16, 2024, 30 pts had been enrolled and received treatment. Median age was 64 years and 73% of pts were male. The most common primary tumor locations were oral cavity (n=10, 33%), oropharynx (n=8, 27%), and larynx (n=6, 20%). Median CPS score was 13.5 (range, 1–101). A median of 4.5 treatment cycles (range 1–15) were received. Treatment-emergent adverse events (TEAEs) occurred in all pts (grade ≥3 in 37%); the most common were fatigue (40%), nausea (27%), cough (23%), and headache (20%). Dazo-related TEAEs occurred in 80% of pts (grade ≥3 in 13%); the most common was fatigue (30%). Cytokine release syndrome was reported in 4 pts (13%; all dazo-related and grade 1–2). TEAEs led to dazo discontinuation in 1 pt. No treatment-related deaths were reported. Among 29 response-evaluable pts, 1 had a confirmed complete response and 7 had confirmed partial responses (+2 unconfirmed), for an ORR of 34%. Median DOR was not reached. Pharmacodynamic analyses revealed biomarker changes consistent with the expected mechanism of action and dose escalation data, including induction of a STING gene signature, cytokine induction, peripheral immune cell activation and CD8+ T cell recruitment to the tumor. Analyses of changes in peripheral ctDNA pre- and post-treatment are ongoing. Conclusions: This early study of dazo 5 mg IV in combination with pembro showed a manageable safety profile with an encouraging ORR in pts with RM-SCCHN. Pharmacodynamic findings demonstrate peripheral and intratumor changes consistent with STING agonism. Clinical trial information: NCT04420884 .