Clinical Trials /

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

NCT04474470

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TYR-219-01
  • NCT ID: NCT04474470

Conditions

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

Interventions

DrugSynonymsArms
NT219Dose escalation of NT219 as a single agent
NT219 and ERBITUX® - Dose EscalationDose escalation of NT219 in combination with ERBITUX®
NT219 and ERBITUX® - ExpansionExpansion cohort of NT219 in combination with ERBITUX®

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of NT219 as a single agentExperimental
  • NT219
Dose escalation of NT219 in combination with ERBITUX®Experimental
  • NT219 and ERBITUX® - Dose Escalation
Expansion cohort of NT219 in combination with ERBITUX®Experimental
  • NT219 and ERBITUX® - Expansion

Eligibility Criteria

        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:

               1. Albumin ≥3 g/dL;

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

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

               4. 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];

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

          5. Stable brain metastases

          6. 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.

          7. 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

         11. Pregnant or lactating women;

         12. Use of known UGT inhibitors within 14 days prior to first dose of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Incidence of treatment emergent adverse events
Time Frame:Up to 24 months
Safety Issue:
Description:Incidence of treatment emergent adverse events with single agent NT219

Secondary Outcome Measures

Measure:Area under the plasma concentration curve [AUC]
Time Frame:Up to 45 days after first study drug administration
Safety Issue:
Description:Area under the plasma concentration curve [AUC] of NT219
Measure:Maximum plasma concentration [Cmax]
Time Frame:Up to 45 days after first study drug administration
Safety Issue:
Description:Maximum plasma concentration [Cmax] of NT219
Measure:Volume of distribution at stead-state [Vss]
Time Frame:Up to 45 days after first study drug administration
Safety Issue:
Description:Volume of distribution at stead-state [Vss] of NT219
Measure:Plasma half-life [t1/2]
Time Frame:Up to 45 days after first study drug administration
Safety Issue:
Description:Plasma half-life [t1/2] of NT219
Measure:Plasma clearance [Cl]
Time Frame:Up to 45 days after first study drug administration
Safety Issue:
Description:Plasma clearance [Cl] of NT219
Measure:Objective Response Rate when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of Response when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Time to Response when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Disease Control Rate when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Progression Free Survival when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Time to Progression when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall Survival when NT219 is used as monotherapy
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Objective Response Rate when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of Response when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Time to Response when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Disease Control Rate when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Progression Free Survival when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Time to Progression when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall Survival when NT219 is used in combination with ERBITUX®
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:TyrNovo Ltd.

Trial Keywords

  • NT219
  • ERBITUX
  • Cetuximab

Last Updated

May 27, 2021