Description:
This study is to assess the safety and tolerability, and to assess the preliminary clinical
benefit of NKTR-214 when combined with pembrolizumab (KEYTRUDA®).
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.
Title
- Brief Title: A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) in Patients With Select Advanced or Metastatic Solid Tumors
- Official Title: A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
16-214-05
- NCT ID:
NCT03138889
Conditions
- Non-Small Cell Lung Cancer
- Melanoma
- Urothelial Carcinoma
- Head and Neck Squamous Cell Carcinoma
- Hepatocellular Carcinoma
Interventions
| Drug | Synonyms | Arms |
|---|
| NKTR-214 | CD122-Biased Cytokine | Dose Optimization, Combo of NKTR-214 +Pembrolizumab(KEYTRUDA®) |
| Pembrolizumab | Keytruda® | Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) |
| NKTR-214 | CD122-Biased Cytokine | Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) |
Purpose
This study is to assess the safety and tolerability, and to assess the preliminary clinical
benefit of NKTR-214 when combined with pembrolizumab (KEYTRUDA®).
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.
Detailed 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 and 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose Optimization, Combo of NKTR-214 +Pembrolizumab(KEYTRUDA®) | Experimental | NKTR-214 will be combined with pembrolizumab | |
| Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) | Experimental | NKTR-214 will be combined with pembrolizumab | |
Eligibility Criteria
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 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 not have progressed within 6 months of receiving radiation, surgery
adjuvant, neoadjuvant, or systemic therapy for cancer treatment.
Dose Optimization Inclusion Criteria (Multiple Solid Tumors):
- Melanoma:
- Histologically confirmed stage III (unresectable) or stage IV (metastatic)
melanoma.
- Non-small Cell Lung Cancer:
- Histologically confirmed stage III (unresectable) or stage IV (metastatic).
- Must not have received systemic anti-PD-L1 therapy for metastatic disease.
- Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma
kinase (ALK) genomic tumor aberrations should have disease progression following
approved targeted therapy as applicable for these aberrations.
- Urothelial Carcinoma:
- Histologically or cytologically documented locally advanced or metastatic
urothelial carcinoma
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- Histologically confirmed diagnosis of recurrent and unresectable or metastatic
HNSCC.
- Hepatocellular Carcinoma (HCC)
- Any radiographic or histologic documentation of locally advanced or metastatic
HCC.
Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):
- Histologically or cytologically confirmed diagnosis of stage IV NSCLC.
- Must not have progressed within 6 months of receiving radiation, surgery, adjuvant,
neoadjuvant, or systemic therapy for cancer treatment.
- Patients with epidermal growth factor receptor (EGFR), c-ros oncogene 1 (ROS1) BRAF
v600e, or anaplastic lymphoma kinase (ALK) genomic tumor aberrations are excluded
- Must not have received anti-cancer therapy for 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 known or suspected 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.
- Chemotherapy or biological therapy within 28 days of therapy. Targeted therapy (e.g.,
tyrosine kinase inhibitors) within 14 days of enrollment
- Participant's inability to adhere to or tolerate protocol or study procedures
- Additional criteria may apply.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) |
| Time Frame: | 100 days after last dose |
| Safety Issue: | |
| Description: | Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to drug discontinuation, and fatal AEs. The overall tolerability of the NKTR-214 in combination with pembrolizumab (Keytruda®) will be evaluated by a Safety Review Committee. |
Secondary Outcome Measures
| Measure: | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) in untreated metatstatic NSCLC. |
| Time Frame: | 100 days after last dose |
| Safety Issue: | |
| Description: | Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and overall tolerability. |
| Measure: | Objective response rate (ORR) per RECIST 1.1 O in in Dose Optimization |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR |
| Measure: | Duration of response (DOR) |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | DOR for patients who have confirmed complete response (CR) or confirmed partial response (PR) as the date from first documented CR or PR to the date of the first objectively documented disease progression per RECIST 1.1 or death due to any cause, whichever is earlier. |
| Measure: | Clinical benefit rate (CBR) |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | CBR is defined as the number of patients with confirmed complete response, confirmed partial response, or stable disease (≥ 7 weeks). |
| Measure: | Time to Response (TTR) |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | TTR will be defined for patients who had confirmed CR or confirmed PR as the time from the date of first dose to date of first documented CR or PR per RECIST 1.1. |
| Measure: | Progression-Free Survival (PFS) |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Overall Survival (OS) |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | OS is defined as the time from date of first dose to the date of death. |
| Measure: | To assess the association between efficacy measures and PD L1 expression in tumors. |
| Time Frame: | Through study completion, an expected average of 2 years |
| Safety Issue: | |
| Description: | Efficacy measures are defined as ORR and changes in PD-L1 expression from on treatment biopsy in Dose Optimization. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Nektar Therapeutics |
Trial Keywords
- NKTR-214
- Metastatic Urothelial Bladder Cancer
- Metastatic Non-Small Cell Lung Cancer
- Pembrolizumab
- Keytruda®
- Melanoma
- Bladder
- NSCLC
- HCC
- HNSCC
- Bempegaldesleukin
- bempeg
Last Updated
October 27, 2020
