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

Trial Status: Active

Patients will receive intra-tumoral (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 bempegaldesleukin. After determination of the recommended Phase 2 dose (RP2D) of NKTR-262, between 6 and 18 patients may be enrolled at the RP2D to further characterize the safety and tolerability profile of the combination of NKTR 262 plus bempegaldesleukin (doublet) or NKTR 262 plus bempegaldesleukin in combination with nivolumab (triplet) in Cohorts A and B, respectively. In the Phase 2 dose expansion portion, patients will be treated with doublet or triplet in the relapsed / refractory setting and earlier lines of therapy.

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), renal cell carcinoma (RCC), colorectal cancer, head and neck squamous cell carcinoma (HNSCC), 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 1-10, 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.


San Diego
University of California San Diego
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Contact: UCSF Clinical Trials
Phone: 877-827-3222


University of Colorado Hospital


Moffitt Cancer Center
Contact: Andrew S. Brohl
Phone: 813-745-3242


Emory University Hospital / Winship Cancer Institute
Status: ACTIVE


Iowa City
University of Iowa / Holden Comprehensive Cancer Center


Kansas City
University of Kansas Cancer Center
Status: ACTIVE


University of Minnesota / Masonic Cancer Center
Status: ACTIVE

New York

Roswell Park Cancer Institute
Status: ACTIVE
New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

North Carolina

Duke University Medical Center
Status: ACTIVE


Case Comprehensive Cancer Center
Status: ACTIVE

South Carolina

Medical University of South Carolina


Vanderbilt University / Ingram Cancer Center


UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
M D Anderson Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

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,

bempegaldesleukin monotherapy increases newly proliferative CD8+ T cells in tumors. NKTR-262

plus bempegaldesleukin is expected to increase expansion of antigen-specific CD8+ T cells. In

preclinical studies, a single IT injection of NKTR-262 plus IV bempegaldesleukin resulted in

complete abscopal effects in tumor models. Preliminary clinical data show bempegaldesleukin

plus nivolumab enhances immune-stimulatory responses. The REVEAL trial will assess safety and

anti-tumor activity of NKTR-262 with bempegaldesleukin +/- nivolumab for the treatment of

selected cancers.

- Melanoma (1st-line and relapsed/refractory)

- Merkel Cell Carcinoma (2nd-line and relapsed/refractory)

- Triple Negative Breast Cancer (1st- and 2nd-line and relapsed/refractory)

- Renal Cell Carcinoma (1st-line and relapsed/refractory)

- Colorectal Cancer (2nd-line and relapsed/refractory; MSI non-high)

- Colorectal Cancer (2nd 3rd-line+, I-O therapy naive; relapsed/refractory; MSI high)

- Head and Neck Squamous Cell Carcinoma (2nd-line and relapsed/refractory)

- Sarcoma (2nd-line and relapsed/refractory)

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization

  • Primary ID 17-262-01
  • Secondary IDs NCI-2018-00619, 2018-004625-84
  • ID NCT03435640