Purple Biotech Ltd. has launched a Phase 2 clinical trial to evaluate NT219, their novel dual-pathway inhibitor, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The study will investigate NT219's potential to overcome tumor resistance when combined with standard treatments pembrolizumab or cetuximab.
The trial, conducted in collaboration with the University of Colorado Anschutz Medical Campus, represents a significant step forward in addressing a critical medical need. Head and neck cancer affects approximately 175,000 new patients annually, making it the sixth most common cancer type, with current standard treatments showing limited efficacy.
Novel Mechanism of Action
NT219 stands out as a first-in-class small molecule drug that simultaneously targets two critical cancer resistance pathways. The compound works by degrading IRS1/2 and blocking IGF1R/IRS1 and STAT3 survival pathways, potentially resensitizing resistant tumors to various treatment modalities.
Dr. Antonio Jimeno, Professor and Director of the Head and Neck Cancer Program at the University of Colorado, who leads the study, explained, "NT219 is a novel and unique compound inhibiting both IRS and STAT3 oncogenic pathways, which are complementary and activated in SCCHN. The combination with standard of care could benefit patients with SCCHN."
Trial Design and Market Potential
The Phase 2 study employs a two-arm design, each following a Simon 2-stage approach:
- Arm 1: NT219 combined with pembrolizumab (anti-PD-1 therapy)
- Arm 2: NT219 combined with cetuximab
Each arm will initially enroll 10 patients, with potential expansion to include an additional 19 patients per arm. The trial builds upon promising Phase 1 results that established NT219's recommended dose and demonstrated anti-tumor activity.
The head and neck cancer treatment market is projected to reach $5 billion by 2030. However, current treatment options show limited effectiveness, with only 20% of patients responding to pembrolizumab and 15-20% to cetuximab, highlighting the significant opportunity for improved therapies.
Preclinical Evidence and Future Impact
Preclinical studies have shown encouraging results, particularly in tumors that developed resistance to PD1 therapy. The combination of NT219 with PD1 inhibition successfully reversed resistance and achieved tumor shrinkage, attributed to the transformation of an immunosuppressive tumor environment into an immunoreactive one.
Gil Efron, Purple Biotech CEO, stated, "NT219 has the potential to establish a new standard of care in combination with pembrolizumab or cetuximab. Purple Biotech remains committed to advancing novel therapeutic strategies that can improve outcomes for patients with aggressive and treatment-resistant cancers."
