ATG-008 Combined With Toripalimab in Advanced Solid Tumors

Phase 1

• Conditions: Advanced Solid Tumor
• Interventions: Drug: ATG-008; Drug: Toripalimab

• Registration Number: NCT04337463
• Lead Sponsor: Sichuan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-21
• Study First Submitted QC: 2020-04-03
• Study First Posted: 2020-04-07
• Study Start: 2020-04-23
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-13
• Last Update Posted: 2021-05-17
• Primary Completion: 2022-05-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Know and voluntarily sign informed consent.

2. Age 18-70 years old (including 18 and 70 years old), weight ≥45 Kg.

3. At least one measurable lesion according to the RECIST 1.1 and RANO evaluation criteria.

4. ECOG performance status score is 0 or 1.

5. Blood chemistry test results, meet the following results:

   1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × normal upper limit (ULN)
   2. Total bilirubin ≤ 1.5 × ULN
   3. Serum albumin> 29 g / L
   4. Creatinine ≤ 1.5 × ULN or 24-hour serum creatinine clearance ≥ 50 mL / min
   5. Lipase and amylase ≤ 2 × ULN.

6. Adequate bone marrow function and meets the following results:

   1. Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L
   2. Platelets ≥ 75 × 10^9 / L
   3. Hemoglobin ≥ 90 g / L.

7. 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).

8. Life expectancy is longer than 3 months.

Exclusion Criteria

1. Have a history of hepatic encephalopathy.
2. Have a thyroid disorder with a clinically significant thyroid dysfunction judged by the investigator (not applicable for thyroid cancer in dose expansion phase).
3. Active or history of upper gastrointestinal bleeding, ulcers, or esophageal varices with bleeding within 6 months.
4. Have a history of HIV infection and/or acquired immunodeficiency syndrome
5. Major surgery has been performed within 4 weeks before the first dose, or is expected during the study period.
6. Have a history of organ transplantation (eg., liver transplantation).
7. Poorly-controlled pleural or pericardial effusion during the screening period.
8. Other primary malignancies occurred within 5 years before the first administration of the study drug with the exception of locally curable malignancies
9. Suffering from active or previously recurring autoimmune diseases or under such a risk.
10. Systemically immunosuppressive drugs are currently used within 14 days of the first dose.
11. 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.
12. Subjects with diabetes or glycated hemoglobin (HbA1c)> 7%.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ATG-008 and Toripalimab	ATG-008	Toripalimab will be combined with ATG-008.
ATG-008 and Toripalimab	Toripalimab	Toripalimab will be combined with ATG-008.

Primary Outcome Measures

Name	Time	Method
ORR	Through study completion (approximately 2 years)	Overall Response Rate
RP2D	Within 21 days after dosing	Recommended phase 2 dose
MTD	Within 21 days after dosing	Maximum Tolerated Dose

Secondary Outcome Measures

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

Trial Locations

Locations (2)

West China of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Chongqing Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China