Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

May 15, 2023 updated by: Nektar Therapeutics

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

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.

Study Overview

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

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • California
      • San Diego, California, United States, 92103
        • University of California, San Diego
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • START Center for Cancer Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
NKTR-255 IV every 21 days
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.
NKTR-255 IV every 21 days
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.
NKTR-255 IV every 21 days
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.
NKTR-255 IV every 21 days
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.
NKTR-255 IV every 21 days
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.
NKTR-255 IV every 21 days
Cetuximab will be given at specified doses on specified days
Other Names:
  • Erbitux®

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.
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
60 days after the last dose of study treatment.
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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.
Through study completion, an expected average of 1 year

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
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.
Through study completion, an expected average of 1 year
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.
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
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
Through study completion, an expected average of 1 year
Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
Through study completion, an expected average of 1 year
Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
Through study completion, an expected average of 1 year
Clearance (CL) for NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
Through study completion, an expected average of 1 year
Volume of Distribution of NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
Through study completion, an expected average of 1 year
Half-life of NKTR-255 and cetuximab
Time Frame: Through study completion, an expected average of 1 year
Through study completion, an expected average of 1 year
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.
Through study completion, an expected average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Study Director, Nektar Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2020

Primary Completion (Actual)

March 30, 2023

Study Completion (Actual)

March 30, 2023

Study Registration Dates

First Submitted

October 30, 2020

First Submitted That Met QC Criteria

October 30, 2020

First Posted (Actual)

November 4, 2020

Study Record Updates

Last Update Posted (Actual)

May 16, 2023

Last Update Submitted That Met QC Criteria

May 15, 2023

Last Verified

May 1, 2023

More Information

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.

Clinical Trials on Cervical Cancer

Clinical Trials on NKTR-255

3
Subscribe