Clinical trial NCT04337463: ATG-008 Combined With Toripalimab in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2020-04-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%.

Primary outcomes:
measure: MTD
timeFrame: Within 21 days after dosing
measure: RP2D
timeFrame: Within 21 days after dosing
measure: ORR
timeFrame: Through study completion (approximately 2 years)
Secondary outcomes:
measure: Cmax
timeFrame: Day 1 - Day 15
measure: AUC
timeFrame: Day 1 - Day 15
measure: DOR
timeFrame: 12 months
measure: DCR
timeFrame: 12 months
measure: PFS
timeFrame: 12 months
measure: OS
timeFrame: 12 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Chengdu
country: China
facility: West China of Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Li Zheng
role: PRINCIPAL_INVESTIGATOR
References: