NT219 Plus Cetuximab Demonstrates Efficacy, Tolerability in SCCHN


NT219 in combination with cetuximab was safe and effective in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.

Michael Schickler, PhD

Michael Schickler, PhD

Treatment with NT219, a first-in-class dual inhibitor of STAT3 and IRS1/2, in combination with cetuximab (Erbitux) displayed a manageable safety profile with anti-tumor activity in patients with HPV-negative recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), according to findings from a phase 1/2 trial (NCT04474470) presented at the 2024 ESMO Targeted Anticancer Therapies Congress.1

At the January 25, 2024, data cutoff, interim findings from the study showed that patients treated with the 2 highest dose levels of NT219 (n = 7) achieved an objective response rate (ORR) of 28.6%, with 2 confirmed partial responses (PR). Additionally, there were 3 instances of stable disease for a disease control rate of 71.4%.

“We were encouraged to see anti-tumor activity in HPV-negative patients,” Michael Schickler, PhD, head, Clinical and Regulatory Affairs, Purple Biotech, said in a press release. “There is an unmet medical need for patients in second- and third-line recurrent/metastatic SCCHN, most of them having HPV-negative disease, with relatively short survival of less than nine months. NT219 should continue to be tested to establish better treatment options for this patient population.”2

The phase 1/2 study enrolled patients with SCCHN who received up to 2 prior regimens for recurrent/metastatic disease and an ECOG performance status of less than 2. NT219 was given at 5 dose levels: 6 mg/kg; 12 mg/kg; 24 mg/kg; 50 mg/kg; and 100 mg/kg. NT219 was administered in combination with cetuximab until disease progression, unacceptable toxicity, patient withdrawal, or death.1

The primary objectives were safety, tolerability, and determination of the recommended phase 2 dose (RP2D) of NT219. Secondary objectives included ORR, duration of response, progression-free survival, overall survival, and pharmacokinetics.

At baseline, the median age in the overall population (n = 17) was 58 years (range, 28-65) and all patients were male. Most patients were White (95%), underwent prior immune checkpoint inhibitor (94%) and platinum-based chemotherapy (82%), had a tumor located in the oral cavity (76%), and negative HPV status (65%). The median number of prior lines of therapy was 2 (range, 1-2); 71% of patients underwent 2 prior lines of therapy.

Additional findings showed that, at a median follow-up of 9.4 months (95% CI, 3.4-10.0), 1 patient who achieved PR at the 50 to 100 mg/kg dose levels was still in response and continuing with treatment; another patient at this dose level was continuing with treatment after experiencing stable disease. At the data cutoff, 8 patients were still alive or had not withdrawn consent.

Study authors highlighted findings from 3 patients. Patient 1 had HPV-negative neck lesions, received frontline cetuximab and radiation and second-line pembrolizumab (Keytruda) plus MCLA-158; this patient experienced a PR per RECIST v1.1 criteria with a 60% decrease in tumor size and withdrew after 6 weeks of treatment with NT219 and cetuximab due to immune-related adverse effects. Patient 2 had HPV-negative neck lesions and received frontline pembrolizumab; this patient experienced a PR of 48% and was still receiving treatment at 40 weeks. Finally, patient 3 had HPV-negative lung lesions, received frontline nivolumab (Opdivo) and second-line pembrolizumab with carboplatin and 5-fluorouracil; this patient experienced stable disease and stayed on treatment for 27 weeks.

In terms of safety, investigators noted that NT219 had a well-tolerated and manageable safety profile up to a dose of 100 mg/kg. The most common any-grade treatment-emergent adverse effects (TEAEs) in the safety population (n = 17) included infusion-related reactions (76.4%), nausea (35.3%), and fatigue (29.4%). Common grade 3 TEAEs consisted of infusion-related reactions (11.8%), hypertension (11.8%), headache (5.9%), and nausea (5.9%). Notably, no grade 4 or 5 TEAEs were observed; the RP2D of NT219 was determined to be 100 mg/kg.

“These positive data support our path forward for NT219 as we plan to initiate a phase 2 study in combination with cetuximab in head and neck cancer in the first half of 2024,” Gil Efron, chief executive officer, Purple Biotech, said in the press release. “We thank the study participants, their families, and clinical researchers for participating in this important study.”2

Disclosures: Dr Rosenberg reported consulting/advisory roles for EMD Serono, Astellas, Eisai, Nanobiotix, Novartis, Regeneron, Vaccitech, Galectin, and Privo.


  1. Rosenberg AJ, Kato S, Johnson D, et al. Interim results of a phase 1/2 trial of NT219 in combination with cetuximab in patients with recurrent/metastatic (r/m) squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol. 2024;9(suppl 1):1-7. doi:10.1016/esmoop/esmoop102270
  2. Purple Biotech presents data of its phase 1 head & neck cancer of NT219 in combination with cetuximab at ESMO TAT Congress 2024. News release. Purple Biotech Ltd. February 27, 2024. Accessed March 18, 2024. https://finance.yahoo.com/news/purple-biotech-presents-data-phase-120000569.html
Related Videos
Sumanta Kumar Pal, MD, FASCO,
Stephen V. Liu, MD
S. Vincent Rajkumar, MD
Bernard A. Fox, PhD
Jameel Muzaffar, MD
Angela Jia, MD, PhD, of University Hospitals
Robert Wang, MD, of Fox Chase Cancer Center
Alexander Kutikov, MD, FACS, of Fox Chase Cancer Center
Roger Li, MD, of Moffitt Cancer Center