Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors

  • STATUS
    Recruiting
  • End date
    Jan 2, 2024
  • participants needed
    240
  • sponsor
    Nektar Therapeutics
Updated on 2 September 2021
Investigator
Nektar Recruitment
Primary Contact
Investigator Site- Fayetteville (7.8 mi away) Contact
+69 other location
cancer
systemic therapy
measurable disease
carcinoma
growth factor
squamous cell carcinoma
lung cancer
BRAF
oximetry
metastasis
pembrolizumab
epidermal growth factor receptor
ROS1
EGFR
brain metastases
pd-l1
cancer treatment
cancer chemotherapy
solid tumour
targeted therapy
epidermal growth factor
squamous cell carcinoma of head and neck
metastatic urothelial carcinoma
immunomodulators
stage iv non-small cell lung cancer
lung carcinoma
immunologic adjuvant
braf v600e mutation
nktr-214
proto-oncogene tyrosine-protein kinase ros

Summary

This study is to assess the safety and tolerability, and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (KEYTRUDA) with or without chemotherapy.

The study is comprised of two groups; dose optimization and dose expansion cohorts.

Dose Optimization will include first-line and second-line melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), and hepatocellular carcinoma (HCC) regardless of PD-L1 expression status. This cohort will include patients enrolled in a 3 + 3 dose escalation and intra-patient step-up dose schemas.

The dose expansion cohort will include first-line NSCLC patients regardless of PD-L1 expression status.

Description

NKTR-214 is a cytokine (investigational agent) that is designed to target CD122, a protein which is found on certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to expand these cells to promote their anti-tumor effects. Pembrolizumab is a programmed death receptor -1 (PD-1) blocking, fully humanized, engineered monoclonal antibody of IgG1 isotype that promotes anti-tumor effects.

The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214 with pembrolizumab with or without chemotherapy. Each dose expansion cohort will enroll approximately 100 new patients.

Dose Optimization: will evaluate an every three-week dose regimen (q3w) of NKTR-214 in combination with pembrolizumab in approximately 40 patients given that the optimal dose and dosing schedule of NKTR-214 in combination with pembrolizumab remains unknown. The previously established recommended Phase 2 dose (0.006 mg/kg) of NKTR-214 was studied in combination with nivolumab. Tumors to be studied include first-line and second-line melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), and hepatocellular carcinoma (HCC). NKTR-214 will be administered at a starting dose of 0.008 mg/kg q3w. Pembrolizumab will be administered at a dose of 200 mg q3w. Patients will undergo a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation at a dose determined by the safety review committee after reviewing the data in the fixed 3+3 dose escalation.

Dose Expansion: NKTR-214 in combination with pembrolizumab in approximately 58 patients will be evaluated in first-line non-small cell lung cancer (NSCLC). The NKTR-214 dose to be studied is 0.006 mg/kg q3w. This dose is based on the recommended phase 2 dose noted in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295) and an ongoing combination trial (16-214-02, NCT02983045). Pembrolizumab will be administered at a dose of 200mg q3w. Following data review for safety and efficacy, additional patients may be dosed using the findings from the dose optimization cohorts.

Details
Condition Non-Small Cell Lung Cancer, Adenocarcinoma, Metastasis, bladder cancer, melanoma, Transitional cell carcinoma, skin cancer, HEPATIC NEOPLASM, HEPATOCELLULAR CARCINOMA, Metastatic Melanoma, Liver Metastases, Bone Metastases, Squamous Cell Carcinoma of the Head and Neck, Brain Metastases, Head and Neck Squamous Cell Carcinoma, Urothelial Cancer, Squamous Cell Carcinoma of Head and Neck, Malignant Melanoma, Liver Cancer, Malignant Adenoma, Metastatic Cancer, Neoplasm Metastasis, Bladder Carcinoma, Urothelial Carcinoma, nsclc, liver cell carcinoma
Treatment Pembrolizumab, Atezolizumab, NKTR-214, Combination of NKTR-214 + atezolizumab
Clinical Study IdentifierNCT03138889
SponsorNektar Therapeutics
Last Modified on2 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Dose Optimization and Dose Expansion Inclusion Criteria
Willing and able to provide written informed consent
Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF)
Life expectancy > 12 weeks from the time of enrollment as determined by the Investigator
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Oxygen saturation 92% on room air for all indications
Measurable disease per RECIST 1.1
Patients with brain metastases are eligible if certain criteria are met
Availability of fresh or archival tumor tissue
Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment
Dose Optimization Inclusion Criteria (Multiple Solid Tumors)
Melanoma
Histologically confirmed stage IV (metastatic) melanoma
Non-small Cell Lung Cancer
Histologically confirmed diagnosis of stage IV NSCLC
Must not have received systemic anti-PD-L1 therapy for metastatic disease
Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed in accordance with standard of care
Urothelial Carcinoma
Histologically confirmed diagnosis of metastatic urothelial carcinoma
Head and Neck Squamous Cell Carcinoma (HNSCC)
Histologically confirmed diagnosis of metastatic HNSCC
Hepatocellular Carcinoma (HCC)
Histologically confirmed diagnosis of metastatic HCC
Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer)
Histologically confirmed diagnosis of stage IV NSCLC
Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment
Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed per standard of care
Must not have received anti-cancer therapy for treatment of metastatic lung cancer
Must not have received prior immunotherapy

Exclusion Criteria

Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s)
Females who are pregnant or breastfeeding
Patients who have an active autoimmune disease
History of allergy or hypersensitivity to study drug components
Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
Prior surgery or radiotherapy within 14 days of therapy
For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded
Participant's inability to adhere to or tolerate protocol or study procedures
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
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