A Phase 1b/2, Open-Label, Multicenter, Dose Escalation And Dose Expansion Study Of Nktr-255 In Combination With Cetuximab As A Salvage Regimen For Solid Tumors
This study is a Phase 1b (Dose Escalation) / 2 (Dose Expansion), open-label, multicenter dose escalation and dose expansion study in patients with relapsed or refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal carcinoma (CRC). The intervention is FDA-approved cetuximab combined with an investigational drug, NKTR-255. Patients will receive a loading dose of cetuximab alone, followed 7 days later by the first combination treatment of cetuximab and NKTR-255 on Cycle 1 Day 1. Thereafter, NKTR-255 will be given in 21-day cycles in combination with weekly IV cetuximab. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255 in combination with cetuximab, this dose of NKTR-255 will be further studied in patients with HNSCC (Cohort A) and CRC (Cohort B) in Phase 2 of the study. Patients will remain on treatment until meeting one of the criteria for discontinuation.
• Histologically confirmed diagnosis of a locally advanced or metastatic HNSCC, CRC, cSCC, ASCC, or cervical cancer.
• Life expectancy > 12 weeks as determined by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Measurable disease per RECIST 1.1. HNSCC:
• Progression on any first or second line platinum-based chemotherapy and/or anti-PD-1 or programmed death-ligand 1 antibody. CRC:
• Patients must have received or were intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease. cSCC
• Patients must have received prior therapy including anti-PD-1 and platinum-based chemotherapy, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy. aSCC
• Patients must have received prior therapy including anti-PD-1 and platinum-based chemotherapy, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy.
• If human immunodeficiency virus (HIV)-positive, patients must also have CD4+ count ≥ 300/μL, undetectable viral load, and be receiving highly active antiretroviral therapy at the time of screening. Cervical Cancer
• Patients must have experienced progression (or toxicity precluding additional treatment) on any first- or second-line platinum-based chemotherapy and anti-PD-(L)1, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy.
• Patients must have known status by pathology for HPV Key
• Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s)
• Prior surgery or radiotherapy within 14 days of initiating study drug(s)
• Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis; active infection requiring systemic therapy within 7 days prior to dosing
• Patients who have been previously treated with IL-2 or IL-15
• Known Grade 3 or 4 hypersensitivity reaction to cetuximab, history of allergy to red meat or tick bites, or history of positive test results for immunoglobulin E antibodies against cetuximab
• Patients who have an active, known, or suspected autoimmune disease NOTE: Other protocol defined inclusion/exclusion criteria may apply
Drug: NKTR-255, Drug: Cetuximab
Head and Neck Squamous Cell Carcinoma, Colorectal Cancer, Cutaneous Squamous Cell Carcinoma, Anal Squamous Cell Carcinoma, Cervical Cancer
HNSCC, Head and Neck Squamous Cell Carcinoma, CRC, Colorectal Cancer, cSCC, Cutaneous Squamous Cell Carcinoma, ASCC, Anal Squamous Cell Carcinoma, Cervical Cancer, NKTR-255, Cetuximab, Erbitux®, Clinics and Surgery Center (CSC), Phase I Clinic