Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

• ClinicalTrials.gov Identifier: NCT04616196
• Recruitment Status: Completed
• First Posted: November 4, 2020
• Last Update Posted: May 16, 2023
• Sponsor: Nektar Therapeutics
• Information provided by (Responsible Party): Nektar Therapeutics

Tracking Information

• First Submitted Date: October 30, 2020
• First Posted Date: November 4, 2020
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: October 30, 2020
• Actual Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2021)

• 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
• 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
• 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
• 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.

Original Primary Outcome Measures (submitted: October 30, 2020)

• Incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) of NKTR-255 with Cetuximab [ 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
• Efficacy of NRTR-255 with Cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]
  Efficacy of NKTR-255 in combination with cetuximab in R/R metastatic HNSCC or CRC by assessing the objective response rate (ORR) by RECIST 1.1

Current Secondary Outcome Measures (submitted: December 21, 2021)

• 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.
• 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.
• 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
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab [ Time Frame: 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 ]
• Clearance (CL) for NKTR-255 and cetuximab [ Time Frame: 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 ]
• Half-life of NKTR-255 and cetuximab [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: October 30, 2020)

Efficacy of NKTR-255 with Cetuximab [ Time Frame: Through study completion, an expected average of 1 year ]

Evaluate the anti-tumor activity of the combination of NKTR-255 and cetuximab by assessing progression-free survival (PFS) and overall survival (OS).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of NKTR 255 in Combination With Cetuximab in Solid Tumors
• 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
• 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.

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
• Study Phase: Phase 1; Phase 2

Study Design

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

Condition

• Head and Neck Squamous Cell Carcinoma
• Colorectal Cancer
• Cutaneous Squamous Cell Carcinoma
• Anal Squamous Cell Carcinoma
• Cervical Cancer

Intervention

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

Study Arms

• Experimental: Dose Escalation of NKTR-255 with Cetuximab
  Establish RP2D, of NKTR-255 with cetuximab.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab
• 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.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab
• 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.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab
• 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.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab
• 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.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab
• 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.
  Interventions:

  • Drug: NKTR-255
  • Drug: Cetuximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 15, 2023): 25
• Original Estimated Enrollment (submitted: October 30, 2020): 78
• Actual Study Completion Date: March 30, 2023
• Actual Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04616196
• Other Study ID Numbers: 19-255-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nektar Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Nektar Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Nektar Therapeutics

• PRS Account: Nektar Therapeutics
• Verification Date: May 2023