MC# 18-24 - A Phase I/II, Open-Label, Multicenter, Dose Escalation and Dose Expansion Study of NKTR-262 in Combination with NKTR-214 and/or Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumor Malignancies

  • Agent(s): NKTR-262, NKTR-214, Nivolumab
  • Disease Type(s): Breast- Triple Negative, Sarcoma, Renal, Ovarian, Melanoma, Colorectal, Merkel Cell, Bladder
  • Phase(s): I, II
  • Drug Classification(s): Targeted Therapy, Cytokines, Immunotherapy, Small Molecule
  • Molecular Target(s): PD-1, TLR, CD122

Mechanism of Action

NKTR-262 is a novel small molecule agonist designed to activate toll-like receptors (TLRs).  Intratumoral delivery of NKTR-262 promotes TLR activation to induce the development of antigen-specific immunity by initiating the process by which the immune system generates antigen-specific cytotoxic T cells to the patient’s specific tumor.

NKTR-214 targets CD122 specific receptors found on the surface of cancer-killing immune cells, known as CD8+ effector T cells. By first generating antigen-specific cytotoxic T cells with NKTR-262 and then growing these CD8+ effector T cells with NKTR-214, the patient’s immunity cycle can potentially be engaged to fight cancer. 

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of the combination of NKTR-214 and NKTR-262 when given with or without Nivolumab
  • How much of NKTR-214 and NKTR-262 and Nivolumab are absorbed into the blood and how fast they are removed when the combination is given with or without Nivolumab
  • If research tests can be used in the future to predict who will benefit from the combination of NKTR-214 and NKTR-262
  • How proteins that indicate the status of your disease are affected with use of the combination of NKTR-214 and NKTR-262 when given with or without Nivolumab
  • If your body develops proteins that work against the combination of NKTR-214 and NKTR-262 when given with or without Nivolumab
  • If the combination of NKTR-214 and NKTR-262, when given with or without Nivolumab, prevents or delays tumor growth or shrinks an existing tumor
Inclusion Criteria
  • Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) metastatic cancer of the following histologies: melanoma (MEL), Merkel cell carcinoma (MCC), triple-negative breast cancer (TNBC), ovarian carcinoma, renal cell carcinoma (RCC), colorectal cancer, urothelial carcinoma, or sarcoma
  • Life expectancy > 12 weeks as determined by the Investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Measurable disease per RECIST 1.1
  • Patients enrolled in Cohorts 1-5, Cohort A, Cohort B and Phase 2 Doublet must be refractory to all therapies known to confer clinical benefit to their disease
  • Fresh tumor tissue available for cellular characterization and programmed cell death protein 1 (PD-L1) status
  • Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies
  • Demonstrated adequate organ function within 14 days of Cycle 1 Day 1 (C1D1)
Exclusion Criteria
  • Use of an investigational agent or an investigational device within 21 days before administration of first dose of study drug(s)
  • Patients treated with prior interleukin-2 (IL-2)
  • Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines
  • Patients who have received systemic interferon (IFN)α within the previous 6 months prior to enrollment to the study
  • Other active malignancy, except non-melanomic skin cancer
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
  • Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.
  • Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening
  • History of unstable or deteriorating cardiac disease within the previous 6 months prior to screening including but not limited to the following:
    • Unstable angina or myocardial infarction
    • Congestive heart failure (NYHA Class III or IV)
    • Uncontrolled clinically significant arrhythmias
  • Need for > 2 antihypertensive medications for management of hypertension (including diuretics)
  • Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration)

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT03435640

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Re: MC# 18-24