A study to investigate the use of the study drug NKTR-214 in combination with other approved treatments for solid tumours.

Phase 1

• Conditions: ocally Advanced or Metastatic Solid Tumor Malignancies; MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003543-11-GB
• Lead Sponsor: ektar Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-04
• Last Update Posted: 13 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1145

Inclusion Criteria

Under Amendment 7, the study is closed to patient screening and enrollment.
For Dose Escalation and Dose Expansion (Parts 1 + 2)
1. Provide written, informed consent to participate in the study and follow study procedures
2. Male/female patients, age 18 years or older at the time of signing ICF
3. Life expectancy >12 weeks
4. Patients must not have received prior IL 2 therapy
5. ECOG performance status 0 or 1
6. Measurable disease per RECIST 1.1
7. Demonstrated adequate organ function, as defined below, within 14 days of treatment initiation
a. WBC count =2000/µL (after at least 7d without growth factor support)
b. ANC =1500/µL (after at least 7d without growth factor support)
c. Platelet count =100 × 103/µL (no transfusions allowed within 7d of C1D1 to meet entry criteria)
d. Hemoglobin = 9.0 g/dL (no transfusions allowed within 7d of C1D1 to meet entry criteria)
e. Serum creatinine = 2 mg/dL (or glomerular filtration rate = 40 mL/min); patients with urothelial carcinoma who are cisplatin ineligible (creatinine clearance < 60 mL/min) may be enrolled if the glomerular filtration rate is = 30 mL/min.
f. AST and ALT = 3× upper limit of normal (ULN)
g. Total bilirubin within normal limits (total bilirubin = 2× ULN if associated with hepatobiliary metastases or Gilbert’s syndrome)
h. Lipase and amylase = 1.5× ULN. Patients with pancreatic metastases and lipase and/or amylase < 3× ULN may enroll. Patients may not enroll if there are clinical or radiographic signs of pancreatitis.
8. A documented LVEF > 45% using standard echocardiogram or MUGA scan test within 60 days prior to Cycle 1 Day 1.
9. Oxygen saturation = 92% on room air
10. Clinically significant toxic effect(s) of the most recent prior anti-cancer therapy must be Grade 1 or resolved (except alopecia and sensory neuropathy); patients with Grade 2 adrenal insufficiency related to prior anti-cancer therapy (defined as requiring medical intervention, such as concomitant steroids) or Grade 2 hypothyroidism (defined as requiring hormone replacement therapy) may be enrolled provided that clinical symptoms are adequately controlled and the daily dose is 10 mg or less of prednisone or equivalent. If the patient received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
11. Women of childbearing potential (WCBP) must agree and commit to the use of to use highly effective methods of birth control throughout the duration of the study until 6 months following the last dose of study drug. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. It is currently unknown whether NKTR-214 may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives should add a barrier method. In certain countries (if permitted by law), WCBP may agree to abide by heterosexual sexual abstinence during the time of participation in this study.
12. Male patients and their female partners of childbearing potential must agree and commit to use a double-barrier contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository) throughout the duration of the study until 6 months following the last dose of study d

Exclusion Criteria

Under Amendment 7, the study is closed to patient screening and
enrollment.
1. Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug
2. Females who are pregnant or breastfeeding
3. Patients who have an active, known or suspected autoimmune disease. Patients requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves’ disease, Hashimoto's disease, alopecia areata, eczema, or with Medical Monitor approval)
4. History of allergy or hypersensitivity to study drug components
5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer. An incidental finding of prostate cancer (identified upon resection of the prostate) is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score = 6, and prostate-specific antigen (PSA) below lower limit of normal by local laboratory.
6. History of organ or tissue transplant that requires systemic use of immune suppressive agents
7. Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
8. Prior surgery or radiotherapy within 14 days of therapy. Patients must have recovered from all radiation-related toxicities and not require corticosteroids.
9. Patients who have had < 28 days since the last chemotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib, erlotinib, gefitinib, afatinib, osimertinib), < 14 days from last dose of hormonal therapy (for patients with breast cancer), or systemic or inhaled steroid therapy at doses greater than 10 mg of prednisone or equivalent before administration of the first dose of study drug.
10. Parts 1 and 2 Patients in whom prior anti PD-1 / anti-PD-L1 therapy was intolerable and required discontinuation of treatment
11. NSCLC patients who require supplemental oxygen
12. Uveal melanoma is excluded
13. Active infection requiring systemic therapy
14. Has known hepatitis B virus (HBV) infection (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C virus (HCV) infection (e.g., HCV ribonucleic acid [RNA] qualitative is detected)
15. Has known immunodeficiency or active human immunodeficiency virus (HIV 1/2 antibodies)
16. Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening
17. History of unstable or deteriorating cardiac disease or cerebrovascular disease within the previous 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. Prior cerebrovascular accident or transient ischemic attack.
18. Need for > 2 antihypertensive medications for management of hypertension (including diuretics)
19. Known current drug or alcohol abuse
20. Any condition including medical, emotional, psychiatric, or logistical th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified