A study to investigate the use of the study drug NKTR-214 in combination with Pembrolizumab for solid tumours
- Conditions
- Patients with with locally advanced or metastatic solid tumors.MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003474-35-IT
- Lead Sponsor
- EKTAR THERAPEUTICS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 98
• Provide written, informed consent to participate in the study and
follow the study procedures.
• Age 18 years or older at the time of signing the informed consent form
(ICF).
• Life expectancy > 12 weeks as determined by the Investigator.
• Patients may have received no more than one prior line of systemic
therapy for locally advanced or metastatic cancer.
• Prior IL-2 therapy is allowed for patients in the dose optimization
cohorts, but not in the dose expansion cohort.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1.
• Oxygen saturation = 92% on room air for all indications; oxygen
saturation = 90% on room air for lung cancer considered to be due to
lung metastasis.
• Measurable disease per RECIST 1.1.
• Patients with hypertension must be on = 2 antihypertensive
medications and without change for the 14 days prior to randomization.
Screening blood pressure must be systolic < 150 mm Hg and < 90 mm
Hg for diastolic blood pressure.
• A brain MRI at Screening is required for all patients with metastatic
NSCLC, and for patients with other tumor types who have known brain
metastasis.
• Patients with brain metastases are eligible if all the criteria below are
fulfilled:
- Brain metastases must be treated at least 2 weeks prior to study
treatment initiation. Treatment may include stereotactic radiosurgery,
whole brain radiotherapy, or neurosurgical resection.
- Brain imaging after treatment and within the screening period must
demonstrate no new or progressing brain metastases.
- No requirement for systemic corticosteroids >10 mg/day prednisone
equivalents. Stable doses of anticonvulsants are allowed.
- No clinically significant symptoms associated with brain metastases.
• Tumor tissue sample is required for all patients. Acceptable samples
include archival tissue obtained no more than 12 months prior to
enrollment if the patient has not received systemic treatment between
the time of biopsy/resection and enrollment. Otherwise, a fresh tumor
biopsy taken during screening is required.
Dose Expansion Cohort (Cohort 2)
1L Non- Small Cell Lung Cancer (Cohorts 2.1, 2.2, and 2.3)
• Histologically or cytologically confirmed diagnosis of NSCLC.
• Patients must have tumor tissue samples available and sent to a
central laboratory for PD-L1 testing using an FDA-approved test or
validated assay. Approximately 20 patients will be enrolled in each
subgroup of PD-L1 negative (PD-L1 < 1%; Cohort 2.1), PD-L1
low/intermediate (PD-L1 1% to 49%; Cohort 2.2) or PD-L1 highly
positive (PD-L1 = 50%; Cohort 2.3).
• Patients with epidermal growth factor receptor (EGFR) or anaplastic
lymphoma kinase (ALK) genomic tumor aberrations are excluded.
• Must not have received anti-cancer therapy for advanced or metastatic
lung cancer.
• Must not have progressed on or within 6 months of completing
adjuvant PD-L1 therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 39
1. Use of an investigational agent or an investigational device within 28
days prior to enrollment.
2. Women who are pregnant or breastfeeding.
3. Patients who have an active, known or suspected autoimmune
disease. Exceptions include patients with type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic
treatment, autoimmune conditions not expected to recur, or with Medical
Monitor approval.
4. History of allergy or hypersensitivity to study drug components.
5. Prior malignancy within the previous 3 years. Exceptions include nonmelanoma
skin cancer and carcinoma in situ of bladder, breast, cervix,
colon, prostate, stomach, and melanoma treated with curative intent,
with minimal risk of recurrence or requiring therapy during study
participation. Patients with prostate cancer are allowed if one of the
following criteria is met:
Stage T2N0M0 or lower; Gleason score = 3+4, and prostate-specific
antigen (PSA) below lower limit of normal by local laboratory.
6. Patients in the dose expansion cohort must not have received prior IL2 therapy.
7. Chronic systemic corticosteroid at >10 mg prednisone or equivalent or
other immunosuppressive agents. Patient on inhaled steroids for asthma
or local steroid injections are allowed.
8. Evidence of clinically significant interstitial lung disease or active,
noninfectious pneumonitis.
9. Surgery or radiotherapy within 14 days of enrollment. Patients who
had surgery or radiotherapy outside of 14 days must have recovered
from associated complications and toxicities.
10. Chemotherapy or biological therapy within 28 days of enrollment.
Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of
enrollment.
11. Prior treatment with immune checkpoint inhibitor.
12. Active infection requiring systemic therapy.
13. Known hepatitis B virus (HBV) infection (e.g., positive hepatitis B
surface antigen [HBsAg]) or hepatitis C virus (HCV) infection (e.g.,
positive HCV ribonucleic acid [RNA]).
14. Known immunodeficiency or active human immunodeficiency virus
(HIV-1/2 antibodies).
15. Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men
and > 470 ms for women at Screening.
16. History of unstable or deteriorating cardiac disease or
cerebrovascular disease within the 2 years prior to screening including
but not limited to the following:
a. Unstable angina or myocardial infarction.
b. Congestive heart failure (New York Heart Association [NYHA] Class
III or IV).
c. Uncontrolled clinically significant arrhythmias.
d. Cerebrovascular accident or transient ischemic attack
17. Current drug or alcohol abuse.
18. Any condition including medical, emotional, psychiatric, or logistical
that, in the opinion of the Investigator, would preclude the patient from
adhering to the protocol or would increase the risk of adverse events
while participating in study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method