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Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

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ClinicalTrials.gov Identifier: NCT04616196
Recruitment Status : Recruiting
First Posted : November 4, 2020
Last Update Posted : April 4, 2022
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Colorectal Cancer Cutaneous Squamous Cell Carcinoma Anal Squamous Cell Carcinoma Cervical Cancer Drug: NKTR-255 Drug: Cetuximab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 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 : October 30, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Erbitux®




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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through study completion, an expected average of 1 year ]
  8. Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  9. Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  10. Clearance (CL) for NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  11. Volume of Distribution of NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  12. Half-life of NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  13. The development of anti-drug antibodies (ADA) against NKTR-255 and cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
    The timing of appearance of anti-NKTR-255 and anti-cetuximab antibodies will be examined.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04616196


Contacts
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Contact: Nektar Recruitment +1-855-482-8676 medicalaffairs@nektar.com
Contact: Medical Affairs medicalaffairs@nektar.com

Locations
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United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92103
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, Iowa
University of Iowa Withdrawn
Iowa City, Iowa, United States, 52242
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Montana
St. Vincent Health Care Recruiting
Billings, Montana, United States, 59101
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
START Center for Cancer Care Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Nektar Therapeutics
Investigators
Layout table for investigator information
Study Director: Study Director Nektar Therapeutics
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Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT04616196    
Other Study ID Numbers: 19-255-03
First Posted: November 4, 2020    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nektar Therapeutics:
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®
Additional relevant MeSH terms:
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Carcinoma
Colorectal Neoplasms
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Head and Neck Neoplasms
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents