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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02740270

Collaborator

(none)

Enrollment

Locations

Arms

43.4

Actual Duration (Months)

10.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Lymphomas	Drug: GWN323 Drug: PDR001	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

92 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 :

Jul 22, 2016

Actual Primary Completion Date :

Mar 3, 2020

Actual Study Completion Date :

Mar 3, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Arm A

Drug: GWN323

Experimental: Arm B

Drug: GWN323

Drug: PDR001

Outcome Measures

Primary Outcome Measures

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

Best Overall Response (BOR), [36 months]
Progression Free Survival (PFS) [36 months]
per irRC and RECIST v1.1 or Cheson (2014)
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]
Presence and titer of anti-GWN323 antibodies [36 months]
Measurement of the effector/regulatory T cell ratio [at screening, 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Chicago	Illinois	United States	60637
2	Novartis Investigative Site	Boston	Massachusetts	United States	02215
3	Novartis Investigative Site	New York	New York	United States	10017
4	Novartis Investigative Site	Houston	Texas	United States	77030
5	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
6	Novartis Investigative Site	Tel Aviv		Israel	6423906
7	Novartis Investigative Site	Kashiwa	Chiba	Japan	277 8577
8	Novartis Investigative Site	Singapore		Singapore	169610
9	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035