Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04616196
• Other study ID #: 19-255-03
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 30, 2020
• Est. completion date: March 30, 2023

Study information

• Verified date: May 2024
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anal Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Squamous Cell
• Cervical Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Cutaneous Squamous Cell Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Uterine Cervical Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	START Center for Cancer Care	San Antonio	Texas
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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
Primary	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	To define the MTD and/or RP2D of NKTR-255 in combination with cetuximab	Through study completion, an expected average of 1 year
Primary	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	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximum Plasma Concentration (Cmax) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Secondary	Area under the concentration-time curve (AUC) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Secondary	Clearance (CL) for NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Secondary	Volume of Distribution of NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Secondary	Half-life of NKTR-255 and cetuximab		Through study completion, an expected average of 1 year
Secondary	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