APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Advanced Solid Tumors

NCT04785196 | Recruiting Phase 1

• 1 other identifier: APG115XC102
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 3

Brief Summary

Part 1 is a phase Ib standard "3 + 3" design, will be employed to determine the MTD of APG-115 by assessing the DLT of APG-115 in combination with PD-1 inhibitor(toripalimab) in advanced solid tumors. Part 2 is a Simon two-stage phase II study design. At RP2D of APG-115 in combination with toripalimab in advanced liposarcoma, approximately 34 patients will be treated with the combination until disease progression, unacceptable toxicity, or another discontinuation criterion is met.

Conditions

Liposarcoma; Advanced Solid Tumor

Keywords

APG-115; Toripalimab; Liposarcoma; Advanced solid tumors

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity (Phase I)

  DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 3 weeks of study treatment. These will be assessed via CTCAE version 5.0.

  21 days

• Recommended Phase II Dose

  Phase I is aimed to generate data to select the recommended Phase II dose.

  21 days

• Overall Response Rate (Phase II)

  Phase II is to assess overall response rate of APG-115 in combination with toripalimab defined as the percentage of subjects with a best overall confirmed CR or a PR at any time as per RECIST v1.1.

  up to 12 months

Study Arms (1)

APG-115+Toripalimab

EXPERIMENTAL

Drug: APG-115; Drug: Toripalimab

Interventions

APG-115 DRUG

Dose escalation of APG-115 in combination with label dose of toripalimab, four dose levels of APG-115 will be tested: 50, 100, 150, and 200mg. APG-115 will be administrated orally every other day (QOD) for consecutive 2 weeks (ie. dosed at Day 1, 3, 5, 7, 9, 11, and 13), with one week dosing off as 3 weeks a cycle.

APG-115+Toripalimab

Toripalimab DRUG

Toripalimab is administrated following CDE approved label dose, i.e.: 240 mg intravenous infusion at Day 1 of every 3 weeks as a cycle.

APG-115+Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent;
• ECOG PS 0-1;
• Phase Ib: Histologically confirmed, advanced liposarcoma or advanced solid tumor patients who failed standard of care therapy; Phase II: Histologically confirmed, advanced liposarcoma with TP53 wide-type and MDM2 Amplification;
• The expected survival period is more than 12 weeks;
• Measurable disease on CT or MRI by RECIST 1.1.
• Adequate bone marrow and organ function as indicated by: the following laboratory values without continuous supportive treatment (such as blood transfusion, coagulation factors and/or platelet infusion, red/white blood cell growth factor administration, or albumin infusion)
• ANC≥1.5 x 10\^9/ L;
• PLT≥100 x 10\^9/ L;
• Hgb≥90 g/L;
• Alb≥30 g/L;
• AST and AST ≤3 \* ULN (for hepatic metastases, ALT and AST≤5\*ULN);
• Serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance (CCr) ≥ 50ml / min.

You may not qualify if:

• Patients who have previously been treated with MDM2-p53 inhibitor;
• Known hypersensitivity reaction to PD-(L)1 inhibitors, or any prior ≥ Grade 3 irAE;
• Prior treatment consisted of any kinds of immunotherapies, like PD-(L)1 inhibitors, anti-PD-L2 antibodies, CTLA-4, OX-40 et.al( for phase II);
• Has known active central nervous (CNS) metastases and/or carcinomatous meningitis;
• Has any active or history of autoimmune disease;
• Active infection or unexplained fever \> 38.5 ° C two weeks before first dose;
• Patients with any severe and/or uncontrolled diseases, including: hypertension and uncontrollable levels of normal anti-hypertensive medication; clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction, unstable or severe angina, or coronary artery bypass surgery, congestive heart failure (New York Heart Association (NYHA) ) \> 2);active or uncontrolled serious infection (≥CTCAE 5.0 Level 2 infection);objective evidence of previous or current history of pulmonary disease; moderate to severe hepatic impairment (Child-Pugh score ≥ 10 points); moderate to severe renal impairment or psychiatric illness/social circumstances that may affect study compliance;
• Poorly controlled arrhythmia (including QTc interval ≥450 ms for males and ≥470 ms for females).

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• Suzhou Yasheng Pharmaceutical Co., Ltd.: collaborator

Study Sites (3)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Cancer Hospital of The University of Chinese Academy of Sciences

Hangzhou, Zhejiang, 310005, China

NOT YET RECRUITING

Shanghai East Hospital (East Hospital affiliated to Tongji University)

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Liposarcoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Ye Guo, MD, PhD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yifan Zhai, MD, PhD

CONTACT

+86-20-28068501; Yzhai@ascentage.com

Guojuan Chen, MD.

CONTACT

+86-20-28068520; guojuan.chen@ascentage.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 5, 2021
• Study Start: May 26, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

CN (3)