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CompletedNCT04616196Updated Jun 8, 2025Results posted

Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

A Phase 1/2 interventional study of NKTR-255 and Cetuximab in Head and Neck Squamous Cell Carcinoma and Colorectal Cancer, sponsored by Nektar Therapeutics. Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-08.

Sponsored by Nektar Therapeutics · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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) and colorectal carcinoma (CRC).

Read the 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.

02

Conditions studied

  • Head and Neck Squamous Cell Carcinoma
  • Colorectal Cancer

Keywords

  • HNSCC
  • Head and Neck Squamous Cell Carcinoma
  • CRC
  • Colorectal Cancer
  • NKTR-255
  • Cetuximab
  • Erbitux®
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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

04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Dose Escalation of NKTR-255 with Cetuximab

    Establish RP2D, of NKTR-255 with cetuximab.

    Drug: NKTR-255 · Drug: Cetuximab

Interventions

  • DrugNKTR-255

    NKTR-255 IV every 21 days

  • DrugCetuximab

    Cetuximab will be given at specified doses on specified days

    Also known as: Erbitux®

05

What researchers measure

Primary outcomes

  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

    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

    Time frame: 60 days after the last dose of study treatment, up to an average of 6 months.

  2. 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

    Time frame: Up to 21 days

06

Results

Posted Jun 8, 2025

Participant flow

Participant flow — Overall Study
MilestoneDose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab
Started8863
Number of participants who were included in the "safety population" analysis.7763
Completed0100
Not completed8763
Withdrew: Progressive disease3041
Withdrew: Death2410
Withdrew: Withdrawal by subject0200
Withdrew: Lost to follow-up1000
Withdrew: Sponsor request2112

Outcome measures

PrimaryIncidence 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

Time frame:
60 days after the last dose of study treatment, up to an average of 6 months.
Reported as:
Count of participants · Participants
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
ParticipantsDose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab
Patients with dose limiting toxicities (DLTs): Infusion related reaction0100
Patients With at Least one TEAE7762
Patients With at Least one TEAE Related to NKTR-2555752
Patients With at Least one Serious TEAE2251
Patients With at Least one Serious TEAE Related to NKTR-2550101
Patients With at Least one TEAE Leading to Death0000
Patients With at Least one TEAE Related to NKTR-255 Leading to Death0000
Patients With at Least one TEAE Leading to NKTR-255 Discontinuation0200
Patients With at Least one TEAE Leading to NKTR-255 Delay, Reduction, or Interruption2020
PrimaryThe 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

Time frame:
Up to 21 days
Reported as:
Number · µg/kg
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
µg/kgDose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab
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 EscalationNANANANA

Adverse events

Collected over Through study completion, up to 6 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With Cetuximab2/8 (25%)2/7 (28.6%)7/7 (100%)
Dose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With Cetuximab4/8 (50%)2/7 (28.6%)7/7 (100%)
Dose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With Cetuximab1/6 (16.7%)5/6 (83.3%)6/6 (100%)
Dose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab1/3 (33.3%)1/3 (33.3%)2/3 (66.7%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventDose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab
Cytokine release syndromeImmune system disorders0/70/70/61/3
CellulitisInfections and infestations0/70/71/60/3
Lung infectionInfections and infestations0/70/71/60/3
SepsisInfections and infestations0/70/71/60/3
Urinary tract infectionInfections and infestations0/70/71/60/3
SyncopeNervous system disorders0/70/71/60/3
Urinary tract obstructionRenal and urinary disorders0/70/71/60/3
PneumoniaInfections and infestations0/70/71/60/3
Small intestinal obstructionGastrointestinal disorders1/70/70/60/3
AstheniaGeneral disorders1/70/70/60/3
Most frequent other events
Showing 10 of 87
Most frequent other events
EventDose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With Cetuximab
Infusion related reactionInjury, poisoning and procedural complications3/76/71/60/3
Dermatitis acneiformSkin and subcutaneous tissue disorders5/74/72/61/3
HypokalaemiaMetabolism and nutrition disorders1/70/73/60/3
Rash maculo-papularSkin and subcutaneous tissue disorders1/70/71/61/3
ChillsGeneral disorders1/71/72/61/3
Influenza like illnessGeneral disorders0/71/71/61/3
NauseaGastrointestinal disorders1/70/72/61/3
DiarrhoeaGastrointestinal disorders0/70/72/60/3
VomitingGastrointestinal disorders0/70/71/61/3
HypomagnesaemiaMetabolism and nutrition disorders1/70/72/60/3

Baseline characteristics

Only 23 participants were dosed with NKTR-255 (7 in Level 1, 7 in Level 2, 6 in Level 3, 3 in Level 4) and are included in the Safety Population analysis used for the remainder of results data.

Age, Continuous
Age, Continuous(years)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
Mean60.7 ± 7.356.9 ± 11.4460.7 ± 18.0259.0 ± 11.0059.3 ± 11.75
Age, Customized
Age, Customized(participants)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
<65543214
>=65 and <7523218
>=75 and <8500101
>=8500000
Sex: Female, Male
Sex: Female, Male(Participants)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
Female02316
Male753217
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
Hispanic or Latino11204
Not Hispanic or Latino564318
Not Reported10001
Unknown00000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
American Indian or Alaska Native00000
Asian00011
Black or African American11002
Native Hawaiian or Other Pacific Islander00000
White455115
Unknown10102
Not Reported11013
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
ECOG PS 0243110
ECOG PS 1533213
Height
Height(centimeter)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
Mean176.69 ± 6.370171.78 ± 7.202167.90 ± 14.675168.54 ± 3.062171.76 ± 9.635
Weight
Weight(kg)Dose Escalation of NKTR-255 Level 1 (1.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 2 (3.0 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 3 (4.5 µg/kg) With CetuximabDose Escalation of NKTR-255 Level 4 (6.0 µg/kg) With CetuximabTotal
Mean91.77 ± 14.41584.20 ± 14.35987.46 ± 44.88470.98 ± 17.72785.63 ± 25.341

1 further baseline measures are reported on the registry.

07

Study locations

6 sites
  • University of California, San Diego
    San Diego, California 92103, United States
  • University of California, San Francisco
    San Francisco, California 94158, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Mary Crowley Cancer Research
    Dallas, Texas 75230, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • START Center for Cancer Care
    San Antonio, Texas 78229, United States
08

References and documents

Study documents

  • Study protocol · Oct 8, 2021
  • Statistical analysis plan · Mar 24, 2023

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04616196
Lead sponsor
Nektar Therapeutics
Responsible party
Sponsor
First posted
Nov 4, 2020
Start date
Oct 30, 2020
Primary completion
Mar 30, 2023
Completion
Mar 30, 2023
Results posted
Jun 8, 2025
Last update
Jun 8, 2025

Study contacts

Study Director
study director · Nektar Therapeutics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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