REVEAL Study of NKTR-262 in Combination With NKTR-214 and Nivolumab in Patients With Locally Advanced / Metastatic Solid Tumor Malignancies — REVEAL  

Colorectal Cancer Clinical Trial

Official title: A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) With or Without Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies

Status Terminated

Clinical Trial Summary

Patients received intratumoral (IT) injections of NKTR-262 in 3-week cycles for up to 3 cycles; bempegaldesleukin with or without nivolumab was administered every 3 weeks (q3w), and treatment continued until unacceptable toxicity, death, or disease progression per RECIST 1.1. Based on Phase 1 results of the study, the decision was made not to start the Phase 2 part of the study and the study was terminated.

Clinical Trial Description

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) ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Renal Cell
• Colorectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Merkel Cell Carcinoma
• Renal Cell Carcinoma
• Sarcoma
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT03435640
• Study type: Interventional
• Source: Nektar Therapeutics
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 15, 2018
• Completion date: May 9, 2022