A Study of NKTR-262 in Combination With NKTR-214 and With NKTR-214 Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies

Status: Active


Patients will receive intratumoral (IT) NKTR-262 in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, NKTR-262 will be combined with systemic administration of NKTR-214. After determination of the recommended Phase 2 dose (RP2D) of NKTR-262, NKTR-262 will be combined with NKTR-214 (Cohort A) and with NKTR-214 plus nivolumab (Cohort B). In the Phase 2 dose expansion portion, patients will be treated with NKTR-262 and NKTR-214 (doublet) or NKTR-262 and NKTR-214 plus nivolumab (triplet) in the relapsed / refractory setting and earlier lines of therapy.

Eligibility Criteria

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. Any liver lesion targeted for injection must not exceed 50 mm at the time of injection.
  • 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.
  • Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).
  • Uveal melanoma will be excluded
  • Patients with tumor that invade the superior vena cava or other major blood vessels.

Locations & Contacts


Moffitt Cancer Center
Status: Active
Contact: Andrew S. Brohl
Phone: 813-745-3242
Email: andrew.brohl@moffitt.org


Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available


University of Minnesota / Masonic Cancer Center
Status: Active
Name Not Available

North Carolina

Duke University Medical Center
Status: Active
Name Not Available

South Carolina

Medical University of South Carolina
Status: In review
Name Not Available


UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
Email: marcella.aguilar@utsouthwestern.edu
M D Anderson Cancer Center
Status: Active
Name Not Available


Fred Hutch / University of Washington Cancer Consortium
Status: In review
Name Not Available

Trial Objectives and Outline

Cancer treatments that couple pharmacological activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a small molecule agonist of toll-like receptors (TLRs) 7/8 designed to be retained in the tumor micro-environment in order to activate antigen-presenting cells (APC), such as dendritic cells, to create new antigen-specific cytotoxic T cells. As a CD122-biased agonist, NKTR-214 monotherapy increases newly proliferative CD8+ T cells in tumors. NKTR-262 plus NKTR-214 is expected to increase expansion of antigen-specific CD8+ T cells. In preclinical studies, a single IT injection of NKTR-262 plus IV NKTR-214 resulted in complete abscopal effects in tumor models. Preliminary clinical data show NKTR-214 plus nivolumab enhances immune-stimulatory responses. The REVEAL trial will assess safety and anti-tumor activity of NKTR-262 with NKTR-214 +/- nivolumab for the treatment of selected cancers. - Melanoma (1st-line and relapsed/refractory) - Merkel Cell Carcinoma (1st -line and relapsed/refractory) - Triple Negative Breast Cancer (1st - and 2nd-line and relapsed/refractory) - Ovarian Cancer (3rd-line and relapsed/refractory) - Renal Cell Carcinoma (1st-line and relapsed/refractory) - Colorectal Cancer (2nd-line and relapsed/refractory) - Urothelial Carcinoma (1st-line and relapsed/refractory) - Sarcoma (2nd-line and relapsed/refractory)

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization

Trial IDs

Primary ID 17-262-01
Secondary IDs NCI-2018-00619
Clinicaltrials.gov ID NCT03435640