27O - Interim results of a phase I/II trial of NT219 in combination with cetuximab in patients with advanced/metastatic squamous cell carcinoma of the head and neck (SCCHN)

Background

NT219 is a small molecule that promotes IRS1/2 degradation and inhibits STAT3 phosphorylation, two major complementary signaling pathways that play a key role in the tumor and its microenvironment. We report interim safety and efficacy results from our phase 1/2 study (NCT04474470) dose escalation of NT219 in combination with cetuximab in patients (Pts) with SCCHN.

Methods

Pts were enrolled in 5 dose level cohorts (6, 12, 24, 50 and 100 mg/kg) of NT219 plus standard dose cetuximab, both administered IV, weekly, until disease progression, unacceptable toxicity, or withdrawal for any other cause. Dose escalation was guided by a 3+3 design with backfilling of additional pts. Primary objectives were safety, tolerability, and recommended phase 2 dose of NT219 with cetuximab.

Results

As of November 27, 2023, 17 pts with R/M SCCHN were enrolled with primary tumor locations including oral cavity (76%), pharynx (18%) and larynx (6%). Pts received a median of 2 prior lines of systemic therapy (range 1-2) for R/M SCCHN, including anti-PD1 (100%), platinum-based chemotherapy (88%) and cetuximab (29%). The most frequent treatment-related adverse events (TRAEs) were infusion reactions (31%), nausea (31%) and rash (25%). G3 TRAEs included hypertension (14%), infusion reaction (7%) and headache (7%); no G4/5 TRAEs were reported. Pharmacokinetic analyses demonstrated dose linearity with exposure at 50mg/kg reaching approximately the level observed in animal models of NT219 plus cetuximab. Indeed, clinical activity was reported in 6 evaluable SCCHN pts treated with 50 & 100mg/kg NT219 and cetuximab for ≥4 weeks. The objective response rate was 33% (2 confirmed PRs) and the disease control rate was 67% (4/6 pts) with all 4 pts having HPV-negative disease who progressed after I/O containing regimens. As of the cutoff date, 5/8 pts (62.5%) treated with the 50 & 100mg/kg NT219, remain on treatment of which 2/4 pts with PR/SD continue treatment for >6 months.

Conclusions

NT219 in combination with cetuximab is well tolerated and exhibits anti-tumor activity in R/M SCCHN pts at dose levels equivalent to animal model effective levels. Enrollment continues and additional data will be presented at the meeting.

Clinical trial identification

NCT04474470.

Editorial acknowledgement

Legal entity responsible for the study

Purple Biotech Ltd.

Funding

Purple Biotech Ltd.

Disclosure

A. Rosenberg: Financial Interests, Personal, Advisory Board: EMD Serono, Novartis, Vaccitech, Eisai, Astellas, Privo, Nanobiotix; Financial Interests, Personal, Invited Speaker: Coherus; Financial Interests, Institutional, Research Grant: Hookipa, BeiGene. D. Johnson: Financial Interests, Personal, Advisory Board, Clinical trial steering committee: Nektar Therapeutics; Financial Interests, Personal, Invited Speaker: Bristol Meyer Squibb, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: Sanofi, Xenthera. R. Geva: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Merck, Medison, Janssen, Pfizer, BMS; Financial Interests, Personal, Advisory Board, 07/2022: AstraZeneca; Financial Interests, Personal, Advisory Board, Ended 3/2022: BOL Pharma; Financial Interests, Personal, Advisory Board: Roche, Ranium, JNJ, Bayer, Oncotest; Financial Interests, Personal, Advisory Board, 06/2022: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses 01/2022: Takeda; Financial Interests, Personal, Other, Travel/Accommodations/Expenses - 06/2022: Medison; Financial Interests, Personal, Other, Options: Pyxis; Financial Interests, Personal, Other, Medical lead: Pyxis. M. Schickler: Financial Interests, Institutional, Full or part-time Employment: Purple Biotech Ltd. H. Reuveni: Financial Interests, Institutional, Full or part-time Employment: Purple Biotech Ltd. All other authors have declared no conflicts of interest.