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Phase I/Ib Study of GWN323 Alone and in Combination With PDR001 in Patients With Advanced Malignancies and Lymphomas

Primary Purpose

Solid Tumors, Lymphomas

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GWN323
PDR001
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumors focused on measuring advanced solid tumors, lymphomas, GWN323, PDR001, advanced malignancies, anti-GITR, anti-PD-1, adults

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with metastatic and/or advanced solid tumors or lymphomas not amenable to curative treatment by surgery.
  • Histologically documented advanced or metastatic solid tumors or lymphomas
  • Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening
  • ECOG Performance Status ≤ 2.

Exclusion Criteria:

  • Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery).
  • Patients diagnosed with T-cell Lymphomas.
  • Patients with prior allogenic transplants.
  • Patients previously treated with anti-GITR therapy.
  • History of severe hypersensitivity reactions to other mAbs.
  • Patients intolerant to prior immunotherapy (unable to continue/receive due to immune-related AE).

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A

Arm B

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) - Single Agent
Dose Limiting Toxicities
Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents
Dose Limiting Toxicities

Secondary Outcome Measures

Best Overall Response (BOR),
Progression Free Survival (PFS)
per irRC and RECIST v1.1 or Cheson (2014)
Serum concentration profiles of GWN323 as a single agent: Cmax
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: Cmax
Presence and titer of anti-GWN323 antibodies
Measurement of the effector/regulatory T cell ratio
Serum concentration profiles of GWN323 as a single agent: AUC
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: AUC
Presence and titer of anti-PDR001 antibodies

Full Information

First Posted
April 5, 2016
Last Updated
February 18, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02740270
Brief Title
Phase I/Ib Study of GWN323 Alone and in Combination With PDR001 in Patients With Advanced Malignancies and Lymphomas
Official Title
A Phase I/Ib Open-label, Multi-center, Dose Escalation Study of GWN323 (Anti-GITR) as a Single Agent and in Combination With PDR001 (Anti-PD-1) in Patients With Advanced Solid Tumors and Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
July 22, 2016 (Actual)
Primary Completion Date
March 3, 2020 (Actual)
Study Completion Date
March 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this trial is to explore the clinical utility of two investigational antibodies in patients with advanced cancer or lymphomas. This is a multi-center, open-label Phase I/Ib study. The study consists of two dose escalation parts and two dose expansion parts testing GWN323 as a single agent or GWN323 in combination with PDR001. The dose escalation parts will estimate the MTD and/or RDE and test different dosing schedules. The dose expansion parts of the study will use the MTD/RDE determined in the dose escalation part to assess the activity, safety and tolerability of the investigational products in patients with specific types of cancer and lymphomas. Approximately 264 adult patients with advanced solid tumors or lymphomas will be enrolled.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Lymphomas
Keywords
advanced solid tumors, lymphomas, GWN323, PDR001, advanced malignancies, anti-GITR, anti-PD-1, adults

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Title
Arm B
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GWN323
Intervention Type
Drug
Intervention Name(s)
PDR001
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicities (DLTs) - Single Agent
Description
Dose Limiting Toxicities
Time Frame
21 days
Title
Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents
Description
Dose Limiting Toxicities
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Best Overall Response (BOR),
Time Frame
36 months
Title
Progression Free Survival (PFS)
Description
per irRC and RECIST v1.1 or Cheson (2014)
Time Frame
36 months
Title
Serum concentration profiles of GWN323 as a single agent: Cmax
Time Frame
36 months
Title
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: Cmax
Time Frame
36 months
Title
Presence and titer of anti-GWN323 antibodies
Time Frame
36 months
Title
Measurement of the effector/regulatory T cell ratio
Time Frame
at screening, 36 months
Title
Serum concentration profiles of GWN323 as a single agent: AUC
Time Frame
36 months
Title
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: AUC
Time Frame
36 months
Title
Presence and titer of anti-PDR001 antibodies
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with metastatic and/or advanced solid tumors or lymphomas not amenable to curative treatment by surgery. Histologically documented advanced or metastatic solid tumors or lymphomas Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening ECOG Performance Status ≤ 2. Exclusion Criteria: Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery). Patients diagnosed with T-cell Lymphomas. Patients with prior allogenic transplants. Patients previously treated with anti-GITR therapy. History of severe hypersensitivity reactions to other mAbs. Patients intolerant to prior immunotherapy (unable to continue/receive due to immune-related AE). Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34389618
Citation
Piha-Paul SA, Geva R, Tan TJ, Lim DW, Hierro C, Doi T, Rahma O, Lesokhin A, Luke JJ, Otero J, Nardi L, Singh A, Xyrafas A, Chen X, Mataraza J, Bedard PL. First-in-human phase I/Ib open-label dose-escalation study of GWN323 (anti-GITR) as a single agent and in combination with spartalizumab (anti-PD-1) in patients with advanced solid tumors and lymphomas. J Immunother Cancer. 2021 Aug;9(8):e002863. doi: 10.1136/jitc-2021-002863.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17796
Description
Study Results

Learn more about this trial

Phase I/Ib Study of GWN323 Alone and in Combination With PDR001 in Patients With Advanced Malignancies and Lymphomas

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