Clinical Trials /

Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

NCT04616196

Description:

Patients with relapsed or refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal carcinoma (CRC) 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 (C1D1). Thereafter, intravenous (IV) 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.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b/2 Study of NKTR 255 in Combination With Cetuximab in Solid Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 19-255-03
  • NCT ID: NCT04616196

Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Colorectal Cancer (CRC)

Interventions

DrugSynonymsArms
NKTR-255CetuximabDose Escalation of NKTR-255 with Cetuximab
NKTR-255CetuximabDose expansion of NKTR-255 with Cetuximab

Purpose

Patients with relapsed or refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal carcinoma (CRC) 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 (C1D1). Thereafter, intravenous (IV) 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.

Detailed Description

      This study is a Phase 1b/2, open-label, multicenter dose escalation and dose expansion study
      in patients with R/R HNSCC or CRC.

      NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation,
      proliferation and promote their anti-tumor effects.

      After an initial cetuximab loading dose during the study run-in period (Day -7), patients
      will receive IV NKTR-255 every 21 days in combination with cetuximab weekly. In the dose
      escalation phase, beginning with Dose Level 1, successive cohorts will receive ascending
      doses of NKTR-255 until the MTD and/or RP2D is determined. Patients who achieve optimal
      response (partial response or complete response), will be given the option to continue
      treatment with NKTR-255 as single agent for maintenance.

      Enrollment into Phase 2 will commence once the RP2D is established in Phase 1b. The RP2D of
      NKTR-255 will be evaluated in expansion Cohorts A and B. Cohort A will combine NKTR-255 and
      cetuximab in patients with R/R HNSCC and Cohort B will combine NKTR-255 and cetuximab in
      patients with R/R CRC.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of NKTR-255 with CetuximabExperimentalEstablish RP2D, of NKTR-255 with cetuximab.
  • NKTR-255
Dose expansion of NKTR-255 with CetuximabExperimentalThe RP2D of NKTR-255 will be evaluated in expansion Cohorts A and B.
  • NKTR-255

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically confirmed diagnosis of a locally advanced or metastatic HNSCC or CRC.

          -  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.

        CRC: Patients with microsatellite instability-high (MSI-H) or mismatched repair disease
        (dMMR) tumors must have been exposed to checkpoint inhibitors such as anti-PD-(L)1 or
        anticytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody.

        Key Exclusion Criteria:

          -  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

          -  Contraindication to or unable to receive cetuximab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) of NKTR-255 with Cetuximab
Time Frame:60 days after the last dose of study treatment.
Safety Issue:
Description:Safety and tolerability of NKTR-255 in combination with cetuximab as evaluated by dose limiting toxicities, incidence of drug-related Adverse Events (AEs), SAEs, and AEs leading to discontinuation, deaths, and clinical laboratory abnormalities per CTCAE 5.0

Secondary Outcome Measures

Measure:Efficacy of NKTR-255 with Cetuximab
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:Evaluate the anti-tumor activity of the combination of NKTR-255 and cetuximab by assessing progression-free survival (PFS) and overall survival (OS).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • HNSCC
  • CRC
  • R/R
  • NKTR-255
  • Cetuximab

Last Updated

October 30, 2020