Refractory Solid Cancer Patients Unexposed to Immunotherapy
Conditions
Brief summary
This is a Phase 2, single-arm, multicenter study, evaluating the anti-tumor efficacy of tumor-infiltrating lymphocyte (TIL) directed tislelizumab monotherapy (also known as BGB-A317) for refractory solid tumors in approximately 72 patients with centrally confirmed T cell inflamed GEP score ≥ 0.857, who have not been previously exposed to immunotherapy. All patients must provide a tumor specimen for T cell inflamed GEP assessment. Archived tissue slide collected within 2 years from the first dose of study drug must be provided. This study will include a Screening Period, a Treatment Period, and a Follow-Up Period. All patients will complete up to 28 days of screening. During the Treatment Period, patients will receive tislelizumab 200 mg fixed dose once every 3 weeks by intravenous (IV) administration until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. After treatment discontinuation, patients will be follow-up for disease progression and survival status until death, withdrawal of consent, or study closure, whichever occurs first. The end of study will be the timepoint when the final data for the study were collected. Additionally, the Investigator Sponsor has the right to terminate this study at any time.
Interventions
T cell inflamed GEP score
Sponsors
Samsung Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥ 20 years at the time of informed consent. 2. Patients with histologically- or cytologically confirmed advanced or metastatic solid tumor who are no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of site physicians, no such treatment is available or indicated according to local or international guidelines. 3. Centrally confirmed T cell inflamed GEP score ≥ 0.857 assessed by RNA sequencing. For baseline T cell inflamed GEP, an archived tissue sample collected within 2 years from the first dose of study drug must be provided. T cell inflamed gene expression profiling will be assessed at a central laboratory. Patients who have at least 1 target lesion per the Response Evaluation Criteria in Solid Tumors (RECIST) Guideline Ver. 1.1 as confirmed by imaging within 28 days before first dose of study drug. 4. ECOG Performance Status Score 0 or 1. 5. Patients with a life expectancy of at least 3 months. 6. Patients with adequate hematological and biological function as indicated by the following screening laboratory values: * Absolute neutrophil count (ANC) ≥ 1.5×109/L * Platelets ≥ 75×109/L * Hemoglobin ≥ 9g/dL or ≥ 5.6 mmol/L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample) * Calculated creatinine clearance ≤ 1.5×upper limit of normal (ULN), or estimated GFR ≥ 60 mL/min by Cockcroft-Gault formula * Serum total bilirubin ≤ 1.5×ULN (total bilirubin must be \< 3×ULN for patients with Gilbert's syndrome) * Aspartate aminotransferase (AST) and ALT ≤ 3×ULN OR ≤ 5×ULN for patients with liver metastases
Exclusion criteria
1. Patients aged ≥ 20 years at the time of informed consent. 2. Patients with histologically- or cytologically confirmed advanced or metastatic solid tumor who are no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of site physicians, no such treatment is available or indicated according to local or international guidelines. 3. Centrally confirmed T cell inflamed GEP score ≥ 0.857 assessed by RNA sequencing. For baseline T cell inflamed GEP, an archived tissue sample collected within 2 years from the first dose of study drug must be provided. T cell inflamed gene expression profiling will be assessed at a central laboratory. Patients who have at least 1 target lesion per the Response Evaluation Criteria in Solid Tumors (RECIST) Guideline Ver. 1.1 as confirmed by imaging within 28 days before first dose of study drug. 4. ECOG Performance Status Score 0 or 1. 5. Patients with a life expectancy of at least 3 months. 6. Patients with adequate hematological and biological function as indicated by the following screening laboratory values: * Absolute neutrophil count (ANC) ≥ 1.5×109/L * Platelets ≥ 75×109/L * Hemoglobin ≥ 9g/dL or ≥ 5.6 mmol/L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample) * Calculated creatinine clearance ≤ 1.5×upper limit of normal (ULN), or estimated GFR ≥ 60 mL/min by Cockcroft-Gault formula * Serum total bilirubin ≤ 1.5×ULN (total bilirubin must be \< 3×ULN for patients with Gilbert's syndrome) * Aspartate aminotransferase (AST) and ALT ≤ 3×ULN OR ≤ 5×ULN for patients with liver metastases Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab | From enrollment to the end of treatment at 30days(+/-7) | ORR is defined as the proportion of patients who had complete response (CR) or partial response (PR) assessed by investigator using RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| iPFS in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | iPFS is defined as the time from first dose of study drug until objective tumor progression per iRECIST or death from any cause, whichever occurs first. |
| ORR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.955 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | — |
| ORR in refractory solid tumor patients with T cell inflamed GEP score ≥ 1.058 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | — |
| OS in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | \- OS is defined as the time from first dose of study drug until death from any cause. |
| PFS in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | PFS is defined as the time from first dose |
| iORR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | iORR is defined as the proportion of patients who had CR or PR assessed by investigator using iRECIST |
| DOR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | DOR is defined as the time from the first determination of an objective response per RECIST v1.1, until objective tumor progression or death from any cause, whichever occurs first. |
| iCBR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | iCBR is defined as the proportion of patients with best overall response of CR and PR, or at least six months of stable disease, per iRECIST. |
| iDOR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857 treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | iDOR is defined as the time from the first determination of an objective response per iRECIST, until objective tumor progression or death from any cause, whichever occurs first. |
| The safety of Tislelizumab in refractory solid tumor patients per NCI CTCAE v5.0 | From enrollment to the end of treatment at 30days(+/-7) | — |
| CBR in refractory solid tumor patients with T cell inflamed GEP score ≥ 0.857treated with Tislelizumab. | From enrollment to the end of treatment at 30days(+/-7) | CBR is defined as the proportion of patients with best overall response of CR and PR, or at least six months of stable disease, per RECIST v1.1. |
Contacts
Primary ContactSehoon Lee, MD, Phd
Outcome results
None listed