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

Phase 1

Completed

• Conditions: Solid Tumors; Lymphomas
• Interventions: Drug: GWN323; Drug: PDR001

• Registration Number: NCT02740270
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-05
• Study First Submitted QC: 2016-04-11
• Study First Posted: 2016-04-15
• Study Start: 2016-07-22
• Primary Completion: 2020-03-03
• Study Completion: 2020-03-03
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-18
• Last Update Posted: 2021-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A	GWN323	-
Arm B	GWN323	-
Arm B	PDR001	-

Primary Outcome Measures

Name	Time	Method
Incidence of Dose Limiting Toxicities (DLTs) - Single Agent	21 days	Dose Limiting Toxicities
Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents	42 days	Dose Limiting Toxicities

Secondary Outcome Measures

Name	Time	Method
Best Overall Response (BOR),	36 months
Serum concentration profiles of GWN323 as a single agent: AUC	36 months
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: AUC	36 months
Presence and titer of anti-PDR001 antibodies	36 months
Progression Free Survival (PFS)	36 months	per irRC and RECIST v1.1 or Cheson (2014)
Presence and titer of anti-GWN323 antibodies	36 months
Serum concentration profiles of GWN323 as a single agent: Cmax	36 months
Serum concentration profiles of GWN323 in combination with PDR001 and derived PK parameters: Cmax	36 months
Measurement of the effector/regulatory T cell ratio	at screening, 36 months

Trial Locations

Locations (1)

Novartis Investigative Site; 🇪🇸 Barcelona, Catalunya, Spain