ATG-008 Combined With Toripalimab in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, single-arm study with dose-escalation and expansion phases to access ATG-008 combined with Toripalimab in patients with advanced solid tumors.

Official Title
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An Open, Dose-escalation and Expansion Study With a Dual TORC1/2 Inhibitor of ATG-008 Combined With PD-1 Antibody of Toripalimab in Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: ATG-008
* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Know and voluntarily sign informed consent. Age 18-70 years old (including 18 and 70 years old), weight ≥45 Kg. At least one measurable lesion according to the RECIST 1.1 and RANO evaluation criteria. ECOG performance status score is 0 or 1. Blood chemistry test results, meet the following results: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × normal upper limit (ULN) Total bilirubin ≤ 1.5 × ULN Serum albumin> 29 g / L Creatinine ≤ 1.5 × ULN or 24-hour serum creatinine clearance ≥ 50 mL / min Lipase and amylase ≤ 2 × ULN. Adequate bone marrow function and meets the following results: Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L Platelets ≥ 75 × 10^9 / L Hemoglobin ≥ 90 g / L. Except for hearing loss and hair loss, all toxicity caused by previous anti-tumor therapy must have returned to ≤ Grade 1 (according to NCI-CTCAE version 5.0). Life expectancy is longer than 3 months. Exclusion Criteria: Have a history of hepatic encephalopathy. Have a thyroid disorder with a clinically significant thyroid dysfunction judged by the investigator (not applicable for thyroid cancer in dose expansion phase). Active or history of upper gastrointestinal bleeding, ulcers, or esophageal varices with bleeding within 6 months. Have a history of HIV infection and/or acquired immunodeficiency syndrome Major surgery has been performed within 4 weeks before the first dose, or is expected during the study period. Have a history of organ transplantation (eg., liver transplantation). Poorly-controlled pleural or pericardial effusion during the screening period. Other primary malignancies occurred within 5 years before the first administration of the study drug with the exception of locally curable malignancies Suffering from active or previously recurring autoimmune diseases or under such a risk. Systemically immunosuppressive drugs are currently used within 14 days of the first dose. The investigator considers that the complications or other situations of the subject may affect compliance with the protocol, or are not suitable for participation in this study. Subjects with diabetes or glycated hemoglobin (HbA1c)> 7%.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG-008 and Toripalimab<br>Toripalimab will be combined with ATG-008. | Drug: ATG-008<br>* Tablet<br>Drug: Toripalimab<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | Maximum Tolerated Dose | Within 21 days after dosing | 
| RP2D | Recommended phase 2 dose | Within 21 days after dosing | 
| ORR | Overall Response Rate | Through study completion (approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak Plasma Concentration (Cmax) | Day 1 - Day 15 | 
| AUC | Area under the plasma concentration versus time curve (AUC) | Day 1 - Day 15 | 
| DOR | Duration from the first observation of at least PR to time of disease progression, or deaths due to disease progression, whichever occurs first. | 12 months | 
| DCR | Disease Control Rate (DCR=CBR+Stable Disease[SD; for a minimum of 12 weeks]) | 12 months | 
| PFS | Duration from start of study treatment to PD or death (regardless of cause), whichever comes first | 12 months | 
| OS | The estimates of Kaplan-Meier | 12 months |