Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

Sponsor
Nektar Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04616196
Collaborator
(none)
326
12
6
45
27.2
0.6

Study Details

Study Description

Brief Summary

This is a Phase 1b/2, open-label multicenter study evaluating NKTR-255 as a monotherapy and together with cetuximab in patients with head and neck squamous cell carcinoma (HNSCC), colorectal carcinoma (CRC), cutaneous squamous cell carcinoma (cSCC), anal cell carcinoma (ASCC) and cervical cancer. The recommended phase 2 dose of NKTR-255, determined in the dose escalation phase (Phase 1b), will be used to treat patients in Phase 2 of this study.

Detailed Description

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

In the dose escalation (Phase 1/b) phase patients with HNSCC or CRC will be treated with ascending doses of NKTR-255 in combination with cetuximab, until the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) is reached. The recommended phase 2 dose of NKTR-255 will be used to treat patients in Phase 2 of this study.

In the dose expansion phase (Phase 2), patients will be treated with NKTR-255 alone and together with cetuximab as follows: Cohort A - HNSCC; Cohort B - CRC; Cohort C - cSCC; Cohort D - ASCC; Cohort E - Cervical Cancer.

Patients who achieve optimal response will be given the option to continue treatment with NKTR-255 as single agent for maintenance.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
326 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase 1: Dose escalation cohorts will be sequential Phase 2: Cohorts A and B will be in parallelPhase 1: Dose escalation cohorts will be sequential Phase 2: Cohorts A and B will be in parallel
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of NKTR-255 Monotherapy or in Combination With Cetuximab as a Salvage Regimen for Solid Tumors
Actual Study Start Date :
Oct 30, 2020
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Aug 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation of NKTR-255 with Cetuximab

Establish RP2D, of NKTR-255 with cetuximab.

Drug: NKTR-255
NKTR-255 IV every 21 days

Drug: Cetuximab
Cetuximab will be given at specified doses on specified days
Other Names:
  • Erbitux®
  • Experimental: Dose Expansion of NKTR-255 with Cetuximab - Cohort A

    The RP2D of NKTR-255 will be evaluated as monotherapy and in combination with cetuximab in patients with HNSCC.

    Drug: NKTR-255
    NKTR-255 IV every 21 days

    Drug: Cetuximab
    Cetuximab will be given at specified doses on specified days
    Other Names:
  • Erbitux®
  • Experimental: Dose Expansion of NKTR-255 with Cetuximab - Cohort B

    The RP2D of NKTR-255 will be evaluated as monotherapy and in combination with cetuximab in patients with CRC.

    Drug: NKTR-255
    NKTR-255 IV every 21 days

    Drug: Cetuximab
    Cetuximab will be given at specified doses on specified days
    Other Names:
  • Erbitux®
  • Experimental: Dose Expansion of NKTR-255 with Cetuximab - Cohort C

    The RP2D of NKTR-255 will be evaluated as monotherapy and in combination with cetuximab in patients with cSCC.

    Drug: NKTR-255
    NKTR-255 IV every 21 days

    Drug: Cetuximab
    Cetuximab will be given at specified doses on specified days
    Other Names:
  • Erbitux®
  • Experimental: Dose Expansion of NKTR-255 with Cetuximab - Cohort D

    The RP2D of NKTR-255 will be evaluated as monotherapy and in combination with cetuximab in patients with ASCC.

    Drug: NKTR-255
    NKTR-255 IV every 21 days

    Drug: Cetuximab
    Cetuximab will be given at specified doses on specified days
    Other Names:
  • Erbitux®
  • Experimental: Dose Expansion of NKTR-255 with Cetuximab - Cohort E

    The RP2D of NKTR-255 will be evaluated as monotherapy and in combination with cetuximab in patients with cervical cancer.

    Drug: NKTR-255
    NKTR-255 IV every 21 days

    Drug: Cetuximab
    Cetuximab will be given at specified doses on specified days
    Other Names:
  • Erbitux®
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) of NKTR-255 in combination with Cetuximab in R/R HNSCC or CRC for Phase 1b Dose Escalation [60 days after the last dose of study treatment.]

      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

    2. Incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) of NKTR-255 monotherapy and in combination with Cetuximab in R/R HNSCC, CRC, cSCC, ASCC, and cervical cancer for Phase 2 Dose Expansion [Through study completion, an expected average of 1 year]

      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

    3. The maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) or NKTR-255 in combination with cetuximab in R/R HNSCC or CRC for Phase 1b Dose Escalation [Through study completion, an expected average of 1 year]

      To define the MTD and/or RP2D of NKTR-255 in combination with cetuximab

    4. Objective Response Rate (ORR) by RECIST 1.1 of NKTR-255 in combination with Cetuximab in R/R metastatic HNSCC or CRC for Phase 2 Dose Expansion [Through study completion, an expected average of 1 year]

      ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

    Secondary Outcome Measures

    1. ORR by RECIST 1.1 of NKTR-255 monotherapy in R/R cSCC, ASCC, and cervical cancer [Through study completion, an expected average of 1 year]

      ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

    2. Overall Survival (OS) of NKTR-255 monotherapy and in combination with Cetuximab [Through study completion, an expected average of 1 year]

      OS is defined as the time from date of first dose to the date of death.

    3. Progression-Free Survival (PFS) of NKTR-255 monotherapy and in combination with Cetuximab [Through study completion, an expected average of 1 year]

      PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause

    4. Change from baseline in immune cell populations (natural killer NK], CD8+ cells, and other immune populations) after administration of NKTR-255 in combination with cetuximab and NKTR-255 monotherapy [Through study completion, an expected average of 1 year]

    5. Change in tumor cells levels after administration of NKTR-255 in combination with cetuximab and NKTR-255 monotherapy [Through study completion, an expected average of 1 year]

    6. Change in cytokine levels after administration of NKTR-255 in combination with cetuximab and NKTR-255 monotherapy [Through study completion, an expected average of 1 year]

    7. Changes in gene expression after administration of NKTR-255 in combination with cetuximab and NKTR-255 monotherapy [Through study completion, an expected average of 1 year]

    8. Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

    9. Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

    10. Clearance (CL) for NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

    11. Volume of Distribution of NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

    12. Half-life of NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

    13. The development of anti-drug antibodies (ADA) against NKTR-255 and cetuximab [Through study completion, an expected average of 1 year]

      The timing of appearance of anti-NKTR-255 and anti-cetuximab antibodies will be examined.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • 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 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Honor Health Scottsdale Arizona United States 85258
    2 University of California, San Diego San Diego California United States 92103
    3 University of California, San Francisco San Francisco California United States 94158
    4 University of Chicago Chicago Illinois United States 60637
    5 University of Iowa Iowa City Iowa United States 52242
    6 Karmanos Cancer Center Detroit Michigan United States 48201
    7 University of Minnesota Minneapolis Minnesota United States 55455
    8 St. Vincent Health Care Billings Montana United States 59101
    9 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    10 Mary Crowley Cancer Research Dallas Texas United States 75230
    11 MD Anderson Cancer Center Houston Texas United States 77030
    12 START Center for Cancer Care San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Nektar Therapeutics

    Investigators

    • Study Director: Study Director, Nektar Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nektar Therapeutics
    ClinicalTrials.gov Identifier:
    NCT04616196
    Other Study ID Numbers:
    • 19-255-03
    First Posted:
    Nov 4, 2020
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Mar 1, 2022

    Study Results

    No Results Posted as of Apr 4, 2022