LiposarcomaPhase 1/2NCT04785196
APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Advanced Solid Tumors
A Phase 1/2 study testing APG-115 and Toripalimab in people with Liposarcoma and Advanced Solid Tumor, run by Ascentage Pharma Group Inc. at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liposarcoma, Advanced Solid Tumor
- What is being tested?
- APG-115 and Toripalimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 3 sitesChina
- Study dates
- 26 May 2021to Jan 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Xing Zhang, M.D.
- Not yet recruiting
Cancer Hospital of The University of Chinese Academy of Sciences
Hangzhou, Zhejiang, 310005
Meiyu Fang, Ph.D
Meiyu Fang, Ph.D
- Recruiting
Shanghai East Hospital (East Hospital affiliated to Tongji University)
Shanghai
Ye Guo, MD, PhD
About this study
Official title: A Phase Ib/II Study of APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Other Advanced Solid Tumors
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.
Read the detailed description
Part 1 is the open label, dose-escalation phase Ib portion of the study to establish an MTD/RP2D of APG-115 in combination with toripalimab. Dose levels/schedule of APG115 will be tested: 50mg, 100mg, 150mg, and 200mg, QOD with 2 weeks on 1 week off as a cycle of 21 days (3 weeks), toripalimab will administrated with label dose.
Part 2 is the phase II portion of the study to evaluate the clinical efficacy and safety of the RP2D of APG-115 in combination with label dose of toripalimab in patients with advanced liposarcoma. In this part, Simon's two-stage design (Simon R (1989). Controlled Clinical Trials 10: 1-10.) will be used. The null hypothesis that the true response rate of combination is 30% or lower will be tested against a one-sided alternative. In the first stage, 19 patients will be accrued. If there are 3 or fewer responses in these patients, the study will be stopped. Otherwise, 15 additional patients will be accrued for a total of 34. The null hypothesis will be rejected if 7 or more responses are observed in 34 patients. This design yields a type I error rate of 0.05 and power of 90%.
- Conditions
- Liposarcoma, Advanced Solid Tumor
- Being tested
- APG-115, Toripalimab
- Keywords
- APG-115, Toripalimab, Liposarcoma, Advanced solid tumors
- Medical subject headings
- Liposarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-115Drug
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.
ToripalimabDrug
Toripalimab is administrated following CDE approved label dose, i.e.: 240 mg intravenous infusion at Day 1 of every 3 weeks as a cycle.
| Study group | Role | What they receive |
|---|---|---|
| APG-115+Toripalimab | Experimental | Not described Receives: Drug: APG-115; Drug: Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 21 days
Recommended Phase II Dose
Phase I is aimed to generate data to select the recommended Phase II dose.
Measured: 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.
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start26 May 2021
- Primary completionApr 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LiposarcomaStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 95 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Ye Guo, MD, PhD, Principal investigator, Shanghai East Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04785196
- Sponsor's protocol ID
- APG115XC102
- Status last verified
- Feb 2025
- First submitted
- 24 Feb 2021
- Last updated
- 26 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of APG-115 in Combination With PD-1 Inhibitor in Patients With Advanced Liposarcoma or Other Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04785196
- Acronym / sponsor ID
- APG115XC102
- Conditions
- Liposarcoma, Advanced Solid Tumor
- Keywords
- APG-115, Toripalimab, Liposarcoma, Advanced solid tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 95 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Study start
- 26 May 2021 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 5 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Part 1 is the open label, dose-escalation phase Ib portion of the study to establish an MTD/RP2D of APG-115 in combination with toripalimab. Dose levels/schedule of APG115 will be tested: 50mg, 100mg, 150mg, and 200mg, QOD with 2 weeks on 1 week off as a cycle of 21 days (3 weeks), toripalimab will administrated with label dose.
Part 2 is the phase II portion of the study to evaluate the clinical efficacy and safety of the RP2D of APG-115 in combination with label dose of toripalimab in patients with advanced liposarcoma. In this part, Simon's two-stage design (Simon R (1989). Controlled Clinical Trials 10: 1-10.) will be used. The null hypothesis that the true response rate of combination is 30% or lower will be tested against a one-sided alternative. In the first stage, 19 patients will be accrued. If there are 3 or fewer responses in these patients, the study will be stopped. Otherwise, 15 additional patients will be accrued for a total of 34. The null hypothesis will be rejected if 7 or more responses are observed in 34 patients. This design yields a type I error rate of 0.05 and power of 90%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APG-115+Toripalimab | Experimental | Drug: APG-115, Drug: Toripalimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APG-115Dose 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. | Drug | APG-115+Toripalimab |
| ToripalimabToripalimab is administrated following CDE approved label dose, i.e.: 240 mg intravenous infusion at Day 1 of every 3 weeks as a cycle. | Drug | APG-115+Toripalimab |
Primary outcome
Dose Limiting Toxicity (Phase I)
Time frame: 21 days
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.
Recommended Phase II Dose
Time frame: 21 days
Phase I is aimed to generate data to select the recommended Phase II dose.
Overall Response Rate (Phase II)
Time frame: up to 12 months
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ye Guo, MD, PhD principal investigator
Shanghai East Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APG-115 and Toripalimab in people with Liposarcoma and Advanced Solid Tumor, run by Ascentage Pharma Group Inc. at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yifan Zhai, MD, PhD (+86-20-28068501, Yzhai@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (Phase I) (time frame: 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2025.