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
- 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 1-8, 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).
- 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.
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
- Primary ID 17-262-01
- Secondary IDs NCI-2018-00619, 2018-004625-84
- Clinicaltrials.gov ID NCT03435640