ATG-008 Combined With Toripalimab in Advanced Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Toripalimab; Drug: ATG-008

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Li Zheng; Phone Number: +86 028-85423655; Email: lzheng2005618@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Recruiting
      • Chongqing Cancer Hospital
      • Contact: Iris Li
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China of Sichuan University
      • Contact: Li Zheng; Phone Number: +86 028-85423655; Email: lzheng2005618@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG-008 and Toripalimab; Toripalimab will be combined with ATG-008.	Drug: Toripalimab; IV infusion; Drug: ATG-008; Tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: Li Zheng, West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 21, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (Actual): April 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ATG-008-HX-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No