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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02740270
Recruitment Status : Recruiting
First Posted : April 15, 2016
Last Update Posted : June 19, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Lymphomas Drug: GWN323 Drug: PDR001 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 264 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 22, 2016
Estimated Primary Completion Date : December 5, 2019
Estimated Study Completion Date : December 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Arm A Drug: GWN323
Experimental: Arm B Drug: GWN323
Drug: PDR001

Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities (DLTs) - Single Agent [ Time Frame: 21 days ]
    Dose Limiting Toxicities

  2. Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents [ Time Frame: 42 days ]
    Dose Limiting Toxicities

Secondary Outcome Measures :
  1. Best Overall Response (BOR), [ Time Frame: 36 months ]
  2. Progression Free Survival (PFS) [ Time Frame: 36 months ]
    per irRC and RECIST v1.1 or Cheson (2014)

  3. Serum concentration profiles of GWN323 as a single agent: Cmax [ Time Frame: 36 months ]
  4. Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: Cmax [ Time Frame: 36 months ]
  5. Presence and titer of anti-GWN323 antibodies [ Time Frame: 36 months ]
  6. Measurement of the effector/regulatory T cell ratio [ Time Frame: at screening, 36 months ]
  7. Serum concentration profiles of GWN323 as a single agent: AUC [ Time Frame: 36 months ]
  8. Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: AUC [ Time Frame: 36 months ]
  9. Presence and titer of anti-PDR001 antibodies [ Time Frame: 36 months ]

Information from the National Library of Medicine

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

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.

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): NCT02740270

Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals +41613241111

United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60637
Contact: Michelle Rainer    773-702-8582   
Principal Investigator: Jason Luke         
United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02215
Contact: Natasha Isaac    617-632-4272   
Principal Investigator: Osama Rahma         
United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10017
Contact: Deepika Cattry    646-227-2178   
Principal Investigator: Alexander Lesokhin         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Rabia Khan    713-563-4667   
Principal Investigator: Sarina Piha-Paul         
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 64239
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277-8577
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT02740270     History of Changes
Other Study ID Numbers: CGWN323X2101
2015-004206-42 ( EudraCT Number )
First Posted: April 15, 2016    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
advanced solid tumors
advanced malignancies

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases