NT219 at the Highest Dose Induces Antitumor Activity in SCCHN

Head and neck cancer : © steph photographies - stock.adobe.com

Antitumor activity was observed in the highest dose cohort treated with NT219 in combination with cetuximab (Erbitux), and 2 of 4 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) demonstrated a partial response, according to interim and preliminary findings from the dose-escalation portion of a phase 1/2 study (NCT04474470).¹

Data showed a dose-dependent increase in drug exposure of NT219, a first-in-class dual inhibitor of insulin receptor substrate (IRS) 1/2 and signal transducer and activator of transcription 3 (STAT3). The exposure reached at the highest dose level of 50 mg/kg was within the efficacy range of the human equivalent dose level. This data followed what was previously predicted in preclinical models.

Patients’ biopsies also demonstrated inhibition of intra-tumoral NT219 targets, including IRS 1/2 and STAT3. Further results from the phase 1/2 study will be provided at an upcoming medical conference.

“We believe these results are very encouraging given the low response rate to cetuximab as monotherapy in recurrent/metastatic SCCHN patients in the second/third line,” said Ari Rozenberg, MD, University of Chicago and study investigator, in a press release. “While still early, we are excited to see responders at the highest NT219 dose level where we expected the appropriate exposure to be attained, along with evidence of on-target treatment effect in patients’ biopsies. I look forward to continuing investigating NT219 and seeing more data in this disease setting with urgent need for improved therapies.”

The open-label, dose-escalation, and dose-expansion, phase 1/2 study is assessing the safety, pharmacokinetics, pharmacodynamics, and efficacy of NT219 as a monotherapy and in combination with cetuximab in patients with R/M SCCHN, or with advanced colorectal cancer.²

Patients 18 years and older are eligible for enrollment in the study if they have at least 1 measurable lesion per RECIST 1.1 with progressing or new lesions since last antitumor therapy, an ECOG performance status score of 0 or 1 at screening and baseline, and stable brain metastases.

The primary end points being evaluated in the study include the incidence of treatment-emergent adverse events and objective response rate (ORR). Secondary end points consist of area under the plasma concentration curve, maximum plasma concentration, volume of distribution at steady-state, plasma half-life, plasma clearance, ORR, duration of response, time to response, disease control rate, progression-free survival, time to progression, and overall survival for NT219 given alone or in combination with cetuximab.

A total of 49 patients were enrolled and treated in 1 of 5 dose levels (3, 6, 12, 24, and 50 mg/kg), with 27 patients included in the monotherapy arm, and 22 in the combination therapy arm.¹ In both cohorts, patients were treated to the highest NT219 dose level of 50 mg/kg.

Overall, NT219 was well-tolerated when administered alone and when given with cetuximab, and no dose-limiting toxicities were reported in the study.

“I am very satisfied with the observed activity of NT219 in recurrent and/or metastatic SCCHN patients. Due to the dire unmet need in this difficult to treat population, we believe that extending these early results through a robust proof of concept study would be meaningful for patients and for Purple Biotech and may lead us to next development steps. We will continue exploring higher dose optimization while designing our next study. We believe that the good tolerability of NT219 in combination with cetuximab can position this combination as a strong candidate to combine with other agents in 2L SCCHN and to achieve better survival for patients,” said Gil Efron, chief executive officer of Purple Biotech, in a press release.

“Additionally, as demonstrated by our preclinical data, we believe that this data could potentially pave the way for development of NT219 in combination with EGFR inhibitors or other agents such as a-PD1 and KRAS inhibitors, potentially unlocking the full potential of NT219,” Efron said.

REFERENCES:

1. Purple Biotech reports positive interim and preliminary results from NT219 phase 1/2 study in R/M head & neck cancer. News release. Purple Biotech Ltd. October 3, 2023. Accessed October 3, 2023. https://tinyurl.com/ycktupem

2. A study to evaluate NT219 alone and in combination with ERBITUX® (cetuximab) in adults with advanced solid tumors and head and neck cancer. ClinicalTrials.gov. Updated December 14, 2022. Accessed October 3, 2023. https://tinyurl.com/t2h9zkdu