Overview

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.

Eligibility

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
11. Pregnant or lactating women;
12. Use of known UGT inhibitors within 14 days prior to first dose of study treatment