A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
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
PhasePhase 1/Phase 2
Lead SponsorTyrNovo Ltd.
Intervention/TreatmentNT219 NT219 and ERBITUX® - Dose Escalation [cetuximab (72813), nt219 (119862)] NT219 and ERBITUX® - Expansion [nt219 (119862), cetuximab (72813)]
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.
Dose escalation of NT219 as a single agent in adult subjects with recurrent and/or metastatic solid tumors
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
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: 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 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; Must have at least 1 measurable lesion per RECIST1.1 with progressing or new lesions since last antitumor therapy; ECOG performance status score of 0 or 1 at screening and baseline Adequate safety lab results: 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; Stable brain metastases 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. 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: Any invasive cancer (other than non-melanoma skin cancer) different from the current disease within 3 years of Screening; 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. Radiation or major surgery within 4 weeks prior to the first dose of NT219; Treatment with another investigational therapy within 30 days or 5 halflives of the drug prior to Screening, whichever is longer 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; Any condition which, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study; History of weight loss >10% over the 2 months prior to Screening; 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 History of active or latent tuberculosis infection Uncontrolled infection HIV, HBV or HCV Pregnant or lactating women; Use of known UGT inhibitors within 14 days prior to first dose of study treatment