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

NCT03435640 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 17-262-012018-004625-84
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 14

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.

Conditions

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

Keywords

Bempegaldesleukin (NKTR-214); NKTR-262; Nivolumab; Opdivo®; Metastatic; Locally advanced; Relapsed/Refractory; TLR7/8; CD122

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Dose-Limiting Toxicities (DLTS)

  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.

  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).

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

  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).

  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.

Study Arms (1)

NKTR-262 + bempegaldesleukin or + bempegaldesleukin with nivolumab

EXPERIMENTAL

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; Drug: bempegaldesleukin; Drug: nivolumab

Interventions

NKTR-262 DRUG

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.

NKTR-262 + bempegaldesleukin or + bempegaldesleukin with nivolumab

bempegaldesleukin DRUG

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.

Also known as: NKTR-214

NKTR-262 + bempegaldesleukin or + bempegaldesleukin with nivolumab

nivolumab DRUG

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.

Also known as: Opdivo®

NKTR-262 + bempegaldesleukin or + bempegaldesleukin with nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (14)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Center, Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Kansas Research Center

Fairway, Kansas, 66205, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Rolig AS, Rose DC, McGee GH, Rubas W, Kivimae S, Redmond WL. Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8+ T cell cytotoxicity over BEMPEG+RT. J Immunother Cancer. 2022 Apr;10(4):e004218. doi: 10.1136/jitc-2021-004218.

  PMID: 35444059 DERIVED

MeSH Terms

Conditions

Melanoma; Carcinoma, Merkel Cell; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Colorectal Neoplasms; Sarcoma; Neoplasm Metastasis; Recurrence

Interventions

bempegaldesleukin; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Neoplasms; Breast Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Connective and Soft Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 19, 2018
• Study Start: March 15, 2018
• Primary Completion: May 9, 2022
• Study Completion: May 9, 2022
• Last Updated: March 8, 2023
• Results First Posted: March 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)