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

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) and colorectal carcinoma (CRC).

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: NKTR-255; Drug: Cetuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • 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

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 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.

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: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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®

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	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, up to an average of 6 months.
The Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NKTR-255 in Combination With Cetuximab in R/R HNSCC or CRC for Phase 1b Dose Escalation	To define the MTD and/or RP2D of NKTR-255 in combination with cetuximab in R/R HNSCC or CRC for Phase 1b Dose Escalation	Up to 21 days

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	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	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	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		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		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		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		Through study completion, an expected average of 1 year
Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Clearance (CL) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Volume of Distribution of NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Half-life of NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
The development of anti-drug antibodies (ADA) against NKTR-255 and cetuximab	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

• Sponsor: Nektar Therapeutics
• Investigators: Study Director: Study Director, Nektar Therapeutics

Study record dates

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): June 8, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Cetuximab; HNSCC; Head and Neck Squamous Cell Carcinoma; CRC; Erbitux®; NKTR-255
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Colonic Diseases; Carcinoma; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Cetuximab
• Other Study ID Numbers: 19-255-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No