Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
NT219 · 2 trials · 7 indications
Objective response rate is defined as the percentage of participants who have confirmed best response of complete response or partial response as determined by the investigator. Response will be assessed by RECIST 1.1 or iRECIST (when applicable, cohort 1 only) at baseline (within 28 days of C1D1) and every 9 weeks +/- 10 days while on treatment. All scans during study intervention will be repeated using the same method (CT, PET-CT, or MRI).
Incidence of treatment emergent adverse events with single agent NT219
Incidence of treatment emergent adverse events with NT219 administered in combination with ERBITUX®
Objective Response Rate when phase 2 dose of NT219 is used in combination with ERBITUX® in adults with recurrent and/or metastatic SCCHN
| Arm | Type | Description |
|---|---|---|
| Cohort 1 NT219 plus pembrolizumab | EXPERIMENTAL | Cohort 1 will enroll patients who have not received PD-1 inhibition in the relapsed/metastatic setting or have received and derived significant clinical benefit from PD-1 inhibition as their first line of therapy. Patients will be treated with NT219 75 mg/kg IV once weekly plus pembrolizumab 200 mg once every three weeks. The first 6 patients will be required to clear a DLT window of 21 days as an abbreviated safety lead-in. |
| Cohort 2 NT219 plus cetuximab | EXPERIMENTAL | Cohort 2 will enroll patients who had progression of disease without clinical benefit from PD-1 inhibition or have received ≥2 prior lines of therapy and are good candidates for cetuximab. Patients will be treated with NT219 75mg/kg IV once weekly plus cetuximab given as an initial loading dose of 400 mg/m2 followed by maintenance dosing of 250 mg/m2 once weekly. |
| Dose escalation of NT219 as a single agent | EXPERIMENTAL | - |
| Dose escalation of NT219 in combination with ERBITUX® | EXPERIMENTAL | - |
| Expansion cohort of NT219 in combination with ERBITUX® | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| NT219 | DRUG | NT219 is a first-in-class small molecule targeting IRS 1/2 and STAT3. Preclinical studies in melanoma have shown NT219 induces PD-L1 expression in vitro and in vivo, resulting in increased efficacy of PD-1 inhibition via synergistic antitumor effect in PD-1 sensitive models and restoration of sensitivity in resistant models. NT219 also synergized with cetuximab in vitro and reversed cetuximab resistance in a head and neck cancer xenograft platform. |
| NT219 and ERBITUX® - Dose Escalation | DRUG | Dose escalation of NT219 in combination with standard dose ERBITUX® in adult subjects with recurrent and/or metastatic squamous cell carcinoma of the head and neck and colorectal adenocarcinoma |
| NT219 and ERBITUX® - Expansion | DRUG | Expansion cohort of NT219 at its RP2D in combination with standard dose ERBITUX® in adult patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck |
Inclusion Criteria: * Age 18 and over. * ECOG PS 0-2. * Incurable head and neck squamous cell carcinoma of mucosal origin (oral cavity, tongue, oropharynx, pharynx, larynx, sinonasal and non-EBV-driven NPC). * Adequate organ and marrow function as defined by routine lab testing including calculated...