NCT03435640

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

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Nektar Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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)

Conditions

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

Interventions

Type	Name	Description
DRUG	NKTR-262	During Phase 1 Doublet: Patients receive escalating doses of NKTR-262 IT (starting dose 0.03 mg) in 3-week treatment cycles. During Phase 1 Doublet (Cohort A), Phase 2 Doublet: Patients were to receive the RP2D of NKTR-262. During Phase 1 Triplet (Cohort B), and Phase 2 Triplet: Patients receive the RP2D of NKTR-262.
DRUG	bempegaldesleukin	During Phase 1 Doublet (Cohort A), and proposed Phase 2 Doublet: Patients receive 0.006 mg/kg bempegaldesleukin administered in 3-week treatment cycles. During Phase 1 Triplet (Cohort B), and proposed Phase 2 Triplet: Patients receive 0.006 mg/kg bempegaldesleukin administered in 3-week treatment cycles.
DRUG	nivolumab	During Phase 1 Triplet (Cohort B), and proposed Phase 2 Triplet: Patients receive a nivolumab flat dose of 360 mg administered in 3-week treatment cycles.

Timeline

• Start date: 2018-03-15
• Primary completion: 2022-05-09
• Completion: 2022-05-09
• First posted: 2018-02-19
• Last updated: 2023-03-08
• Results posted: 2023-03-08

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study