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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors, Lymphomas

Intervention / Treatment
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* Drug: GWN323
* Drug: PDR001


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: GWN323<br> <br> |
| Experimental: Arm B<br> | Drug: GWN323<br> <br> Drug: PDR001<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities (DLTs) - Single Agent | Dose Limiting Toxicities | 21 days | 
| Incidence of Dose Limiting Toxicities (DLTs) - Combination Agents | Dose Limiting Toxicities | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR), |  | 36 months | 
| Progression Free Survival (PFS) | per irRC and RECIST v1.1 or Cheson (2014) | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumors, lymphomas, GWN323, PDR001, advanced malignancies, anti-GITR, anti-PD-1, adults