Combining APG-115 with PD-1 inhibitor for advanced liposarcoma and solid tumors

A Phase Ib/II Study of APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Other Advanced Solid Tumors

This study is testing if combining a new drug called APG-115 with a PD-1 inhibitor can safely help people with advanced liposarcoma and other solid tumors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 95 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: toripalimab
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT04785196 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of APG-115 in combination with the PD-1 inhibitor toripalimab in patients with advanced liposarcoma or other advanced solid tumors. The study is divided into two parts: the first part aims to determine the maximum tolerated dose (MTD) of APG-115 using a dose-escalation approach, while the second part evaluates the clinical efficacy of the established dose in a larger cohort of patients. Participants will be monitored for disease progression and treatment-related toxicities throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed advanced liposarcoma or solid tumors that have not responded to standard therapies.

Not a fit: Patients with non-advanced tumors or those who have not failed standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced liposarcoma and solid tumors who have exhausted standard treatment options.

How similar studies have performed: Other studies have shown promise in using PD-1 inhibitors in combination with novel agents for treating advanced cancers, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent;
2. ECOG PS 0-1;
3. 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;
4. The expected survival period is more than 12 weeks;
5. Measurable disease on CT or MRI by RECIST 1.1.
6. 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)

   1. ANC≥1.5 x 10\^9/ L;
   2. PLT≥100 x 10\^9/ L;
   3. Hgb≥90 g/L;
   4. Alb≥30 g/L;
   5. AST and AST ≤3 \* ULN (for hepatic metastases, ALT and AST≤5\*ULN);
   6. Serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance (CCr) ≥ 50ml / min.

Exclusion Criteria:

1. Patients who have previously been treated with MDM2-p53 inhibitor;
2. Known hypersensitivity reaction to PD-(L)1 inhibitors, or any prior ≥ Grade 3 irAE;
3. 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);
4. Has known active central nervous (CNS) metastases and/or carcinomatous meningitis;
5. Has any active or history of autoimmune disease;
6. Active infection or unexplained fever \> 38.5 ° C two weeks before first dose;
7. 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;
8. Poorly controlled arrhythmia (including QTc interval ≥450 ms for males and ≥470 ms for females).

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Cancer Hospital of The University of Chinese Academy of Sciences — Hangzhou, Zhejiang, China (Not_yet_recruiting)
• Shanghai East Hospital (East Hospital affiliated to Tongji University) — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Ye Guo, MD, PhD — Shanghai East Hospital
• Study coordinator: Yifan Zhai, MD, PhD

Conditions Liposarcoma; Advanced Solid Tumor; APG-115; Toripalimab; Advanced solid tumors