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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03435640
Recruitment Status : Terminated (Based on the overall results from the Phase 1 part of the study the sponsor decided to end the study. The decision was not due to safety reasons.)
First Posted : February 19, 2018
Results First Posted : March 8, 2023
Last Update Posted : March 8, 2023
Information provided by (Responsible Party):
Nektar Therapeutics

Brief 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.

Condition or disease Intervention/treatment Phase
Melanoma Merkel Cell Carcinoma Triple Negative Breast Cancer Head and Neck Squamous Cell Carcinoma Renal Cell Carcinoma Colorectal Cancer Sarcoma Drug: NKTR-262 Drug: bempegaldesleukin Drug: nivolumab Phase 1 Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 15, 2018
Actual Primary Completion Date : May 9, 2022
Actual Study Completion Date : May 9, 2022

Arm Intervention/treatment
Experimental: NKTR-262 + bempegaldesleukin or + bempegaldesleukin with nivolumab
Phase 1: NKTR-262 in escalating doses, combined with bempegaldesleukin. The goal of this dose escalation part of the study is to establish a recommended Phase 1b dose for NKTR-262 + bempegaldesleukin with nivolumab, followed by a dose-confirmation cohort.
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.

Other Name: NKTR-214

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.
Other Name: Opdivo®

Primary Outcome Measures :
  1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTS) [ Time Frame: The DLT window is 21 days following NKTR-262 single agent administration (Cycle 1) and an additional 9 days when combined with bempeg for staggered dosing administration (Cohorts 1 and 2), or 7 days for the same day administration (Cohort 3 and higher). ]

    DLTs were assessed in Cohort 1 through Cohort 9, which had dose levels of NKTR-262 as 0.03mg, 0.06mg, 0.06mg, 0.12mg, 0.24mg, 0.48mg, 0.96mg, 1.92mg, and 3.84mg in combination with bempegaldesleukin (bempeg).

    There was only 1 DLT that occurred in one of the Cohort 9 patients. Therefore, the maximum tolerated dose (MTD) of NKTR 262 was not reached.

  2. Objective Response Rate (ORR) Per RECIST 1.1 in Cohort A and Cohort B at Recommended Phase 2 Dose (RP2D) [ Time Frame: From Cycle 1 Day 1 to 100 days after the last dose of study drug or the date for new anti-cancer therapy, whichever is earlier. ]

    Objective Response Rate (ORR) per RECIST 1.1 in Cohort A and Cohort B at Recommended Phase 2 Dose (RP2D).

    ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and as assessed by Blinded Independent Central Review (BICR).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key 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).

Key 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.

Additional general and tumor specific inclusion and exclusion criteria will apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03435640

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United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Center, Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Kansas
University of Kansas Research Center
Fairway, Kansas, United States, 66205
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Nektar Therapeutics
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Study Director: Study Director Nektar Therapeutics
  Study Documents (Full-Text)

Documents provided by Nektar Therapeutics:
Study Protocol  [PDF] April 9, 2020
Statistical Analysis Plan  [PDF] February 10, 2022

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Nektar Therapeutics Identifier: NCT03435640    
Other Study ID Numbers: 17-262-01
2018-004625-84 ( EudraCT Number )
First Posted: February 19, 2018    Key Record Dates
Results First Posted: March 8, 2023
Last Update Posted: March 8, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nektar Therapeutics:
Bempegaldesleukin (NKTR-214)
Locally advanced
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Carcinoma, Squamous Cell
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Head and Neck Neoplasms
Polyomavirus Infections
DNA Virus Infections