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Clinical Trial 19480

Cancer Type: Multiple
Study Type: Treatment
NCT#: NCT03435640

Phase: Phase I/II
Prinicipal Investigator: Andrew Brohl

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Overview

Study Title

The Reveal Study: A Phase 1/2, Open-Label, Multicenter, Dose Escalation And Dose Expansion Study Of Nktr-262 In Combination With Bempegaldesleukin (Nktr-214) And In combination With Bempegaldesleukin (Nktr-214) Plus Nivolumab In Patients With Locally Advanced Or Metastatic Solid Tumor Malignancies

Summary

This is an investigational study of a drug called NKTR-262 that will be given together with a drug called NKTR-214 and also possibly another drug called Opdivo® (nivolumab). NKTR-262, also referred to as "Study Drug A", is an investigational drug. The purpose of this study is to test the safety, tolerability, and effectiveness (how well these drugs work together) of the Study Drug A (NKTR-262) and Study Drug B (NKTR-214) given together ("Doublet therapy"), or of the Study Drug A and Study Drug B given with Study Drug C ( Opdivo®) ("Triplet therapy").

Objective

The Primary Objectives are: To evaluate the safety and tolerability, and define the maximum tolerated dose (MTD) or RP2D of NKTR-262 in combination with NKTR-214 (doublet) and the safety and tolerability of NKTR-262 and NKTR-214 plus nivolumab (triplet). To evaluate the anti-tumor activity of the combination of NKTR-262 plus NKTR-214 (doublet) and the combination of NKTR-262 and NKTR-214 plus nivolumab (triplet) by assessing the objective response rate (ORR) by RECIST 1.1. The Secondary Objectives are: To evaluate the anti-tumor activity of the combination of NKTR-262 plus NKTR-214 (doublet) and the combination of NKTR-262 and NKTR-214 plus nivolumab (triplet) by assessing progression-free survival (PFS) and overall survival (OS). To evaluate the proportion of patients with an abscopal response by RECIST 1.1 assessed 9 weeks after the initiation of treatment of NKTR-262 plus NKTR-214 or NKTR-262 and NKTR-214 plus nivolumab. The Exploratory Objectives are: To evaluate the efficacy of the combination of NKTR-262 and NKTR-214 (doublet) and the combination of NKTR-262, NKTR-214 and nivolumab (triplet) by assessing ORR by immune-related RECIST (irRECIST). To assess the effects of the combination of NKTR-262 and NKTR-214 (doublet) and of the combination of NKTR-262 and NKTR-214 plus nivolumab (triplet) on immune cells in blood and tumor. To characterize the pharmacokinetics (PK) of NKTR-262, NKTR-214 and their metabolites, and nivolumab when administered in combination. To assess the immunogenicity of NKTR-214 and nivolumab when given in combination with NKTR-262. To assess the association between efficacy measures and PD-L1 expression in tumors. To assess the association between anti-tumor activity and immune cells in tumor and blood. To assess the association between efficacy measures and tumor mutational burden (TMB) in tumors and blood. To assess the effect of NKTR-262 on QT/QTc interval using exposure response analysis.

Treatments

Therapies

Medications

BMS-936558 (Nivolumab); NKTR-214 (Bempegaldesleukin); NKTR-262 (); Nivolumab (Opdivo)

Inclusion Criteria

  • Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) metastatic cancer of the following histologies: MEL, MCC, TNBC, RCC, CRC, head and neck squamous cell carcinoma, or sarcoma.
  • Age 18 years or older
  • 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.
  • Participants enrolled in Cohorts 1-5, 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 with preferably one of the lesions injected to be a draining lymph node [if identified as an injectable tumor where an IT injection can be given]) 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).
  • Other criteria apply

  • 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 IL-2.
  • Have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.
  • Have received systemic interferon (IFN)α within the previous 6 months prior to enrollment to the study.
  • Has a known additional malignancy that is progressing or requires active treatment. Some exceptions apply.
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
  • Prior surgery or radiotherapy within 14 days of initiating study drug(s). 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
  • Need for > 2 antihypertensive medications for management of hypertension (including diuretics).
  • History of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).
  • Additional exclusions apply

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