Clinical trial NCT02740270: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lymphomas
Keywords: advanced solid tumors
lymphomas
GWN323
PDR001
advanced malignancies
anti-GITR
anti-PD-1
adults
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-04-15
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) - Single Agent
timeFrame: 21 days
measure: Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents
timeFrame: 42 days
Secondary outcomes:
measure: Best Overall Response (BOR),
timeFrame: 36 months
measure: Progression Free Survival (PFS)
timeFrame: 36 months
measure: Serum concentration profiles of GWN323 as a single agent: Cmax
timeFrame: 36 months
measure: Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: Cmax
timeFrame: 36 months
measure: Presence and titer of anti-GWN323 antibodies
timeFrame: 36 months
measure: Measurement of the effector/regulatory T cell ratio
timeFrame: at screening, 36 months
measure: Serum concentration profiles of GWN323 as a single agent: AUC
timeFrame: 36 months
measure: Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: AUC
timeFrame: 36 months
measure: Presence and titer of anti-PDR001 antibodies
timeFrame: 36 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.