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

Sponsor
TyrNovo Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04474470
Collaborator
(none)
83
Enrollment
7
Locations
3
Arms
35.9
Anticipated Duration (Months)
11.9
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: NT219
  • Drug: NT219 and ERBITUX® - Dose Escalation
  • Drug: NT219 and ERBITUX® - Expansion
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
83 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study With Open-Label, Dose Escalation Phase Followed by Single-Arm Expansion at the Maximum Tolerated Dose to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of NT219 Injection Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
Actual Study Start Date :
Sep 3, 2020
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose escalation of NT219 as a single agent

Drug: NT219
Dose escalation of NT219 as a single agent in adult subjects with recurrent and/or metastatic solid tumors
Experimental: Dose escalation of NT219 in combination with ERBITUX®

Drug: NT219 and ERBITUX® - Dose Escalation
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
Experimental: Expansion cohort of NT219 in combination with ERBITUX®

Drug: NT219 and ERBITUX® - Expansion
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

Outcome Measures

Primary Outcome Measures

  1. Part 1: Incidence of treatment emergent adverse events [Up to 24 months]

    Incidence of treatment emergent adverse events with single agent NT219

  2. Part 2: Incidence of treatment emergent adverse events [Up to 24 months]

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

  3. Part 3: Objective Response Rate [Up to 24 months]

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

Secondary Outcome Measures

  1. Area under the plasma concentration curve [AUC] [Up to 45 days after first study drug administration]

    Area under the plasma concentration curve [AUC] of NT219

  2. Maximum plasma concentration [Cmax] [Up to 45 days after first study drug administration]

    Maximum plasma concentration [Cmax] of NT219

  3. Volume of distribution at stead-state [Vss] [Up to 45 days after first study drug administration]

    Volume of distribution at stead-state [Vss] of NT219

  4. Plasma half-life [t1/2] [Up to 45 days after first study drug administration]

    Plasma half-life [t1/2] of NT219

  5. Plasma clearance [Cl] [Up to 45 days after first study drug administration]

    Plasma clearance [Cl] of NT219

  6. Objective Response Rate when NT219 is used as monotherapy [Up to 24 months]

  7. Duration of Response when NT219 is used as monotherapy [Up to 24 months]

  8. Time to Response when NT219 is used as monotherapy [Up to 24 months]

  9. Disease Control Rate when NT219 is used as monotherapy [Up to 24 months]

  10. Progression Free Survival when NT219 is used as monotherapy [Up to 24 months]

  11. Time to Progression when NT219 is used as monotherapy [Up to 24 months]

  12. Overall Survival when NT219 is used as monotherapy [Up to 24 months]

  13. Objective Response Rate when NT219 is used in combination with ERBITUX® [Up to 24 months]

  14. Duration of Response when NT219 is used in combination with ERBITUX® [Up to 24 months]

  15. Time to Response when NT219 is used in combination with ERBITUX® [Up to 24 months]

  16. Disease Control Rate when NT219 is used in combination with ERBITUX® [Up to 24 months]

  17. Progression Free Survival when NT219 is used in combination with ERBITUX® [Up to 24 months]

  18. Time to Progression when NT219 is used in combination with ERBITUX® [Up to 24 months]

  19. Overall Survival when NT219 is used in combination with ERBITUX® [Up to 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Subject with previously treated advanced solid tumors (Portion 1) or recurrent and/or metastatic squamous cell carcinoma of the head and neck (Portion 2 and 3) or colorectal adenocarcinoma, stage III/IV (Portion 2) that must have failed or not be a candidate for available standard of care therapies with documented progression/intolerance following the most recent prior regimen;

  2. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new lesions since last antitumor therapy;

  3. ECOG performance status score of 0 or 1

  4. Adequate safety lab results:

  5. Albumin ≥3 g/dL;

  6. Bilirubin ≤1.5 times the upper limit of normal (ULN) or <3 times the ULN in the case of Gilbert Syndrome;

  7. Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and alkaline phosphatase <3 times the ULN;

  8. 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];

  9. White blood cell (WBC) count ≥2000/uL; hemoglobin ≥9 g/dL;

  10. Stable brain metastases

  11. Subjects must have a "wash out" period of at least 4 weeks prior to first study drug administration from all previous chemotherapy and experimental agents except for anti-CTLA4, anti-PD-L1, anti-PD-1 antibodies and IL-2 which must have a "wash out" period of at least 6 weeks prior to first study drug administration, and all adverse events (AEs) have either returned to baseline or stabilized at Grade 1 or less.

  12. WCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test, WCBP must agree to abstain from sex or use an adequate method of contraception, males must abstain from sex with WCBP or use an adequate method of contraception

Exclusion Criteria:

  1. Any invasive cancer (other than non-melanoma skin cancer) different from the current disease within 3 years of Screening;

  2. Known hypersensitivity to epidermal growth factor receptor (EGFR), Janus kinase (JAK), or signal transducer and activator of transcription (STAT) antagonists/inhibitors, or inactive ingredients of NT219.

  3. Radiation or major surgery within 4 weeks prior to the first dose of NT219;

  4. Treatment with another investigational therapy within 30 days or 5 halflives of the drug prior to Screening, whichever is longer

  5. Active, untreated central nervous system (CNS) metastases;

  6. Severely immunocompromised as defined by white blood cell (WBC) count <2000/mm3 and or CD4+ lymphocyte count ≤200/mm3;

  7. Major surgery within 4 weeks of study administration;

  8. Any condition which, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study;

  9. History of weight loss >10% over the 2 months prior to Screening;

  10. Clinically relevant serious co-morbid medical conditions, including:

  • Active infection; history of active or latent tuberculosis infection

  • Cardiovascular (e.g., History of long QT syndrome, NYHA) Class III or IV cardiac disease)

  • Pulmonary (e.g., GOLD score ≥3, chronic obstructive, chronic restrictive pulmonary disease)

  • Active CNS disease including carcinomatous meningitis;

  • Psychiatric illness/social situation that would limit compliance with study requirements;

  • Prior organ allograft;

  • Subjects with active, known or suspected autoimmune disease

  • Uncontrolled infection HIV, HBV or HCV

  1. Pregnant or lactating women;

  2. Use of known UGT inhibitors within 14 days prior to first dose of study treatment

Contacts and Locations

Locations

Site City State Country Postal Code
1 California Cancer Associates for Research and Excellence Encinitas California United States 92024
2 The Angeles Clinic and Research Institute Los Angeles California United States 90025
3 UCSD Moores Cancer Center San Diego California United States 92037
4 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
5 The University of Chicago and Biological Sciences Chicago Illinois United States 60637
6 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
7 Stephenson Cancer Center Oklahoma City Oklahoma United States 73117

Sponsors and Collaborators

  • TyrNovo Ltd.

Investigators

  • Study Director: Michael Schickler, PhD, TyrNovo Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
TyrNovo Ltd.
ClinicalTrials.gov Identifier:
NCT04474470
Other Study ID Numbers:
  • TYR-219-01
First Posted:
Jul 16, 2020
Last Update Posted:
May 3, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by TyrNovo Ltd.
NT219
ERBITUX
Cetuximab
Additional relevant MeSH terms:
Neoplasms
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Cetuximab

Study Results

No Results Posted as of May 3, 2022