- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04616196
Study of NKTR 255 in Combination With Cetuximab in Solid Tumors
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Nektar Recruitment
- Phone Number: +1-855-482-8676
- Email: medicalaffairs@nektar.com
Study Contact Backup
- Name: Medical Affairs
- Email: medicalaffairs@nektar.com
Study Locations
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California
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San Diego, California, United States, 92103
- University of California, San Diego
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San Francisco, California, United States, 94158
- University of California, San Francisco
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Texas
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Dallas, Texas, United States, 75230
- Mary Crowley Cancer Research
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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San Antonio, Texas, United States, 78229
- START Center for Cancer Care
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Escalation of NKTR-255 with Cetuximab
Establish RP2D, of NKTR-255 with cetuximab.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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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.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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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.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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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.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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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.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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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.
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NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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
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60 days after the last dose of study treatment.
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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
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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
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Through study completion, an expected average of 1 year
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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
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To define the MTD and/or RP2D of NKTR-255 in combination with cetuximab
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Through study completion, an expected average of 1 year
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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
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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.
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Through study completion, an expected average of 1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Through study completion, an expected average of 1 year
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Overall Survival (OS) of NKTR-255 monotherapy and in combination with Cetuximab
Time Frame: Through study completion, an expected average of 1 year
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OS is defined as the time from date of first dose to the date of death.
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Through study completion, an expected average of 1 year
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Progression-Free Survival (PFS) of NKTR-255 monotherapy and in combination with Cetuximab
Time Frame: Through study completion, an expected average of 1 year
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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
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Through study completion, an expected average of 1 year
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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
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Through study completion, an expected average of 1 year
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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
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Through study completion, an expected average of 1 year
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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
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Through study completion, an expected average of 1 year
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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
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Through study completion, an expected average of 1 year
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Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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Through study completion, an expected average of 1 year
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Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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Through study completion, an expected average of 1 year
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Clearance (CL) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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Through study completion, an expected average of 1 year
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Volume of Distribution of NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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Through study completion, an expected average of 1 year
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Half-life of NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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Through study completion, an expected average of 1 year
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The development of anti-drug antibodies (ADA) against NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
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The timing of appearance of anti-NKTR-255 and anti-cetuximab antibodies will be examined.
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Through study completion, an expected average of 1 year
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, Nektar Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplasms, Squamous Cell
- Uterine Cervical Neoplasms
- Carcinoma
- Colorectal Neoplasms
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Cetuximab
Other Study ID Numbers
- 19-255-03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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