Patients with with locally advanced or metastatic solid tumors. MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: bempegaldesleukin
Product Code: NKTR-214
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: bempegaldesleukin
Current Sponsor code: NKTR-214
Other descript
Sponsors
Nektar Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 from the time of enrollment as determined by the Investigator. • In the dose optimization cohorts, patients may have received no more than 1 prior line of systemic therapy for metastatic cancer. A "line of therapy" is defined as any regimen – single-agent or combination therapy, cytotoxic therapy, immuno-oncology therapy separately or in combination – that is given in a non-palliative setting and is stopped for progression of disease. • Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment. • Prior IL-2 therapy is allowed for patients in the dose optimization cohorts who have completed therapy, and who have reported no severe ADRs or had all ADRs completely resolved. Prior IL-2 therapy is not allowed for patients in the dose expansion cohorts. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. • Oxygen saturation = 90% on room air. • 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 10 mg/day prednisone equivalents at therapy initiation. 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. • For France only: enrolled patients must be affiliated to a Social Security System. Dose Expansion Cohorts (Cohorts 2, 3, 4 and 5) 1L Non- Small Cell Lung Cancer (Cohorts 2, 3, 4 and 5) • Histologically confirmed diagnosis of Stage IV NSCLC. • Tumor tissue sample is required to be submitted to the central lab for all patients prior to enrollment. 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. A tracking number confirming shipment of the sample to the central laboratory must be supplied prior to Cycle 1 Day 1. Within each subgroup, this is : PD-L1 negative (PD-L1 < 1%; Cohort 2.1): 20 response-evaluable patients, PD-L1 low/intermediate (PD-L1 1% to 49%; Cohort 2.2): 18 response-evaluable patients or PD-L1 highly positive (PD-L1 = 50%; Cohort 2.3): 20 response-evaluable patients. - For Franc
Exclusion criteria
Exclusion criteria: 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 autoimmune disease. Exceptions include patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or autoimmune conditions not expected to recur. 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, 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 cohorts must not have received prior immunotherapy or IL-2 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 or topical steroids 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. For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (eg, tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded. 11. For Dose Expansion Cohorts: Patients with ongoing AEs related to prior cancer therapies will be excluded. 12. Active infection requiring systemic therapy/ Active 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]). 13. Known immunodeficiency or active human immunodeficiency virus (HIV-1/2 antibodies). 14. Known active SARS-CoV2 infection with confirmed test report. 15. For France only: received a live vaccine within 30 days prior to the first dose of the study. 16. For France only: known history of active tuberculosis (TB: Bacillus tuberculosis). 17. Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening. 18. Known cardiovascular history, including cerebrovascular disease within the 12 months 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 (CVA) or transient ischemic attack (TIA). e. History of pulmonary embolism (PE), deep vein thrombosis (DVT), or venous or non-CVA/TIA arterial thromboembolic event within 3 months prior to enrollment. • Patients with a history of a venous or arterial thromboembolic event must be asymptomatic prior to enrollment and must be receiving a stable regimen of therapeutic anticoagulation (low molecular weight heparin [LMWH] or direct oral anticoagulation [DOAC]) or had received appropriate treatment as indicated by the regional clinical guidelines. Additionally: • Use of coumadin is permitted;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the ORR per blinded independent central review (BICR) by RECIST 1.1 of NKTR-214 plus pembrolizumab with or without systemic chemotherapy in patients with untreated metastatic NSCLC.;Secondary Objective: • To evaluate safety and tolerability of NKTR-214 plus pembrolizumab with or without systemic chemotherapy in patients with untreated NSCLC (Dose Expansion only). • To assess the preliminary efficacy (per BICR)of NKTR-214 in combination with pembrolizumab with or without systemic chemotherapy: - objective response rate (ORR) by RECIST 1.1 (dose optimization only) - duration of response (DOR) by RECIST 1.1 - clinical benefit rate (CBR) by RECIST 1.1 - time to response (TTR) by RECIST 1.1 - progression-free survival (PFS) by RECIST 1.1 - overall survival (OS) • To assess the association between efficacy measures and PD-L1 expression in tumors.;Primary end point(s): Primary Endpoint : - ORR by RECIST 1.1 of NKTR-214 plus pembrolizumab in patients with untreated metastatic NSCLC ;Timepoint(s) of evaluation of this end point: screening then every 9 weeks (± 7 days) from Cycle 1 Day 1, EOT (unless scan done within 4 weeks) and at the 90-day long-term follow-up visits | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Efficacy: screening then every 9 weeks (± 7 days) from Cycle 1 Day 1, EOT (unless scan done within 4 weeks) and at the 90-day long-term follow-up visits Safety: Throughout the study;Secondary end point(s): Efficacy endpoints : Tumor response evaluation : o duration of response (DOR) by RECIST 1.1 o clinical benefit rate (CBR) by RECIST 1.1 o time to response (TTR) by RECIST 1.1 o progression-free survival (PFS) by RECIST 1.1 o overall survival (OS) Secondary Safety endpoints : incidence of adverse events (AEs), including serious AEs (SAEs) • clinical laboratory tests (blood and urine sampling) • vital signs • physical examination | — |
Countries
Australia, France, Germany, Italy, Spain, United States
Contacts
Public ContactClinical Trial Information Desk
Nektar Therapeutics
Outcome results
None listed