Abstract B002: A first-in-human, first-in-class, phase 1 trial of QEQ278 in patients with advanced solid tumors

Abstract Background: QEQ278 is a first-in-class, investigational fusion protein targeting natural killer group 2D (NKG2D). QEQ278 aims to drive the killing of NKG2D ligand (NKG2D-L)-expressing tumor cells through ADCC/ADCP and neutralize soluble NKG2D-L to re-sensitize NK cells/cytotoxic T-lymphocytes. QEQ278 has shown a favorable safety profile in preclinical toxicology studies. Here, we report the early clinical findings of QEQ278 from the ongoing dose-escalation part of the first-in-human study in patients (pts) with advanced solid tumors. Methods: This is an ongoing phase 1/1b, open-label, multi-center, dose-escalation/-expansion trial (NCT05462873) in adult pts with advanced/metastatic non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), renal cell carcinoma (RCC), and human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Eligible pts had histologically confirmed advanced malignancies and exhausted standard of care therapies. QEQ278 was administered intravenously at doses 70 mg, 210 mg, 700 mg, and 1400 mg every 2 weeks (Q2W). Primary objectives of dose escalation were to evaluate the safety and tolerability, and to determine the maximum tolerated dose and recommended dose for expansion (RDE). Secondary objectives were to assess antitumor activity, immunogenicity, and pharmacokinetics. Results: As of September 9, 2024, a total of 30 pts with ESCC (10, 33.3%), RCC (8, 26.7%), HNSCC (3, 10.0%), and NSCLC (9, 30.0%) had been treated with QEQ278. At data cutoff, 26 (86.7%) pts discontinued treatment, mainly due to progressive disease (20, 66.7%). Per RECIST v1.1, no objective responses were observed at the time of data cutoff, and 7 (23.3%) pts had stable disease. The median exposure to QEQ278 for all treated pts was 8 weeks (range: 2 to 42 weeks). 2 pts experienced dose limiting toxicities (1 pt experienced grade 3 cytokine release syndrome at 700 mg Q2W, and the other pt experienced a grade 3 infusion-related reaction [IRR] at 1400 mg Q2W). Adverse events (AEs) were reported in 28 (93.3%) pts, of which 15 (50.0%) pts had grade ≥3 AEs. Treatment-related AEs (TRAEs) were reported in 16 (53.3%) pts, with 7 (23.3%) pts experiencing grade ≥3 TRAEs. The most commonly reported TRAEs were IRRs (9, 30.0%) and chills (3, 10.0%). Serious AEs (SAEs) were reported in 11 (36.7%) pts and grade ≥3 SAEs were reported in 9 (30.0%) pts. The most common SAE was dyspnea reported in 2 (6.7%) pts. 12 deaths were reported, 3 while on treatment; none were assessed as related to QEQ278. The cause of death was disease progression (n=11; ESCC, 6 pts; HNSCC, 1 pt; NSCLC, 2 pts; RCC, 2 pts) and acute pancreatitis (1 pt). Pharmacokinetic, immunogenicity, and biomarker data will be included in the presentation. Conclusions: Early clinical data of QEQ278 monotherapy reported an acceptable safety profile in pts with advanced solid malignancies. Further dose exploration is required to establish a RDE and assess preliminary antitumoral activity. Citation Format: Christophe Le Tourneau, Martin Schuler, Massimo A. Di Nicola, Yick Ching Justina Lam, Yasutoshi Kuboki, Chia-Chi Lin, Jean-Pascal Machiels, Justin F. Gainor, Zev A. Wainberg, Manish R. Patel, Javier A. Otero, Kimberly Ann. Kornbluth, Rebhi Bsharat, Jaya Pisupati, Thiruvamoor Ramkumar, Anwesha Chaudhury, Arjun Oberoi. A first-in-human, first-in-class, phase 1 trial of QEQ278 in patients with advanced solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B002.