Lymphomas, Solid Tumors
Conditions
Keywords
advanced solid tumors, lymphomas, GWN323, PDR001, advanced malignancies, anti-GITR, anti-PD-1, adults
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.
Interventions
DRUGGWN323
DRUGPDR001
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| Measurement of the effector/regulatory T cell ratio | at screening, 36 months | — |
| Progression Free Survival (PFS) | 36 months | per irRC and RECIST v1.1 or Cheson (2014) |
Countries
Canada, Israel, Japan, Singapore, Spain, United States
Outcome results
None listed