A Study to Evaluate NT219 Alone and in Combination with ERBITUX® (Cetuximab) in Adults with Advanced Solid Tumors and Head and Neck Cancer

NCT04474470 | Completed Phase 1 FDA Drug

• 1 other identifier: TYR-219-01
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 10

Brief Summary

This is a phase 1/2, multi-center study with an open-label, dose escalation phase followed by a single-arm expansion phase to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 alone and in combination with ERBITUX® (cetuximab) in adults with recurrent and/or metastatic solid tumors.

Conditions

Solid Tumor, Adult; Squamous Cell Carcinoma of Head and Neck; Colorectal Adenocarcinoma; Metastatic Solid Tumor; Recurrent Solid Tumor; Head and Neck Cancer

Keywords

NT219; ERBITUX; Cetuximab

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of treatment emergent adverse events

  Incidence of treatment emergent adverse events with single agent NT219

  Up to 24 months

• Part 2: Incidence of treatment emergent adverse events

  Incidence of treatment emergent adverse events with NT219 administered in combination with ERBITUX®

  Up to 24 months

• Part 3: Objective Response Rate

  Objective Response Rate when phase 2 dose of NT219 is used in combination with ERBITUX® in adults with recurrent and/or metastatic SCCHN

  Up to 24 months

Secondary Outcomes (19)

• Area under the plasma concentration curve [AUC]

  Up to 45 days after first study drug administration

• Maximum plasma concentration [Cmax]

  Up to 45 days after first study drug administration

• Volume of distribution at stead-state [Vss]

  Up to 45 days after first study drug administration

• Plasma half-life [t1/2]

  Up to 45 days after first study drug administration

• Plasma clearance [Cl]

  Up to 45 days after first study drug administration

Study Arms (3)

Dose escalation of NT219 as a single agent

EXPERIMENTAL

Drug: NT219

Dose escalation of NT219 in combination with ERBITUX®

EXPERIMENTAL

Drug: NT219 and ERBITUX® - Dose Escalation

Expansion cohort of NT219 in combination with ERBITUX®

EXPERIMENTAL

Drug: NT219 and ERBITUX® - Expansion

Interventions

NT219 DRUG

Dose escalation of NT219 as a single agent in adult subjects with recurrent and/or metastatic solid tumors

Dose escalation of NT219 as a single agent

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

Dose escalation of NT219 in combination with ERBITUX®

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

Expansion cohort of NT219 in combination with ERBITUX®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject with previously treated colorectal or head and neck cancer with documentation of incurable locally advanced, recurrent and/or metastatic squamous cell carcinoma of the head and neck or colorectal adenocarcinoma, stage III/IV that must have failed or not be a candidate for available standard of care therapies and not deemed amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy) by a multidisciplinary committee to include an oncologist, surgeon, and radiation oncologist
• Subjects with head and neck cancer should have received up to 2 previous regimens for recurrent/metastatic disease; Only subjects with documented wild-type KRAS and BRAF colorectal cancer are allowed to enroll; subjects with colorectal cancer should have received up to 3 previous regimens for metastatic disease.
• Subjects with HPV negative status only to be enrolled (for subjects with head and neck cancer)
• Completion of curative radiation therapy at least 4 weeks prior to study treatment initiation; For subjects with head and neck cancer - prior focal palliative radiotherapy must be completed at least 2 weeks prior to study drug administration
• Availability of archival tumor samples prior to treatment initiation; When not available or feasible for any reason, this requirement can be waived after discussion with the Sponsor.
• Fresh tumor biopsy should be obtained unless deemed by the investigator that the procedure may pose a risk of bleeding to the subject or otherwise deemed not medically safe and/or feasible for any reason. This biopsy must be either formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue samples, obtained within 3 months prior to enrollment and after the last systemic treatment was completed, with an associated pathology report. Biopsy should be excisional, incisional or core needle. Fine needle aspiration biopsy of the involved neck lymph nodes is permitted however, fine needle aspiration or biopsies of bone lesions that do not have a soft tissue component are unacceptable for submission.
• Must have at least 1 measurable lesion per RECIST1.1 with progressing or new lesions since last antitumor therapy.
• Age ≥18 years at the time of signing ICF;
• ECOG performance status score of \<2 at Screening and Baseline (Day 0);
• Adequate safety lab results at Screening and at Baseline (Day 0) for those tests that require repeating at Baseline, including the following:
• Albumin ≥3 g/dL
• Bilirubin ≤1.5 times the upper limit of normal (ULN) or \<3 times the ULN in the case of Gilbert Syndrome
• Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and alkaline phosphatase \<3 times the ULN
• Creatinine clearance \>60 mL/minute based on the Cockcroft-Gault equation \[creatinine clearance in mL/min = (140 - age in years) x body weight (kg)/72 x serum creatinine (mg/dL); multiplied by 0.85 for women\]
• White blood cell (WBC) count ≥2000/uL; hemoglobin ≥9 g/dL;

You may not qualify if:

• Nasal, paranasal sinus, or nasopharyngeal carcinoma and mutated KRAS colorectal adenocarcinoma, aside from World Health Organization (WHO) Type I and II \[keratinizing, non-Epstein-Barr virus (EBV) positive\] nasopharyngeal carcinoma which will be allowed;
• In Study Part 2: For subjects with HNSCC: Received more than 2 prior systemic regimens for their HNSCC; For subjects with CRC: Received more than 3 prior systemic regimens for their CRC; In Study Part 3: For subjects with HNSCC: Received more than 2 prior regimens for their recurrent/metastatic HNSCC
• Received cetuximab as part of the most recent regimen and/or within the last 6 months prior to study registration
• Any invasive cancer (other than non-melanoma skin cancer) different from the current disease within 3 years of Screening
• Known hypersensitivity to ERBITUX® or other epidermal growth factor receptor (EGFR), Janus kinase (JAK), or signal transducer and activator of transcription (STAT) antagonists/inhibitors, or inactive ingredients of NT219 Injection.
• Radiation or major surgery within 4 weeks prior to the first dose of NT219;
• Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer
• Parenteral vitamin C administration and oral supplements containing vitamin C
• History of weight loss \>10% over the 2 months prior to Screening
• Active, untreated central nervous system (CNS) metastases
• Severely immunocompromised as defined by white blood cell (WBC) count \<2000/mm3 and/or CD4+ lymphocyte count ≤200/mm3
• Major surgery within 4 weeks of study administration;
• Known allergy to tick bites or red meat, or known immunoglobulin E (IgE) antibodies directed against galactose-α-1,3-galactose
• Any condition which, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study
• Clinically relevant serious co-morbid medical conditions including, but not limited to:

Sponsors & Collaborators

• TyrNovo Ltd.: lead

Study Sites (10)

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

UCSD Moores Cancer Center

San Diego, California, 92037, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

The University of Chicago and Biological Sciences

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73117, United States

Location

Hadassah University Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Sourasky Medical Center

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Schickler, PhD

  TyrNovo Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 16, 2020
• Study Start: September 3, 2020
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3); US (7)