Patients With Advanced Solid Tumor or LymphomaPhase 1APG-115NCT02935907
APG-115 in Patients With Advanced Solid Tumors or Lymphomas
A Phase 1 study testing APG-115 in people with Patients With Advanced Solid Tumor or Lymphoma, run by Ascentage Pharma Group Inc. at 2 sites in United States.
Trial summary
APG-115 is a novel, orally active small-molecule mouse double minute 2 homolog (MDM2) inhibitor. Mechanistically, APG-115 increases p53 and p21 overexpression, activates p53 - mediated apoptosis in tumor cells retaining wild-type p53. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Advanced Solid Tumor or Lymphoma
- What is being tested?
- APG-115
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to 28 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or no standard treatment is available. Only patients with advanced/metastatic cancer who have disease progression after treatment with all available therapies that are known to confer clinical benefit.
- Male or non-pregnant, non-lactating female patients age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- Adequate hematologic and bone marrow functions
- Adequate renal and liver function
- Troponin (I) ≤ Upper Limit of Normal
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- Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function \& no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug.
- Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug.
- Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
- Willingness and ability to comply with study procedures and follow-up examination.
- Willingness to provide and there is confirmed availability of pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing fresh tumor biopsy is optional for subjects in dose escalation cohorts.
- Willingness to undergo tumor genotyping for P53 mutation at screening. Confirmation of P53 non-mutant status is encouraged, but not required.
Who cannot join
- Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti estrogen analogs, agonists required to suppress serum testosterone levels); or any investigational therapy within 14 days prior to the first dose of study drug.
- Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug.
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 2.
- Has gastrointestinal conditions that could affect the absorption of APG-115 in the opinion of the Investigator.
- Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted.
- Received a biologic (granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor or erythropoietin) within 14 days prior to the first dose of study drug.
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- Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
- Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
- Neurologic instability per clinical evaluation due to tumor involvement of the central nervous system (CNS). Patients with CNS tumors that have been treated, are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for > 28 days may be enrolled.
- Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).
- Diagnosis of fever and neutropenia within 1 week prior to study drug administration.
- Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
- Prior treatment with MDM2 inhibitors.
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
START Midwest
Grand Rapids, Michigan, 49546
The START Center for Cancer Care
San Antonio, Texas, 78229
About this study
Official title: A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-115 in Patients With Advanced Solid Tumors or Lymphomas
APG-115 is a novel, orally active small-molecule mouse double minute 2 homolog (MDM2) inhibitor. Mechanistically, APG-115 increases p53 and p21 overexpression, activates p53 - mediated apoptosis in tumor cells retaining wild-type p53. APG-115 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft and a patient derived xenograft (PDX) models. The preclinical data generated from APG-115 suggest that it may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-115 is intended for the treatment of patients with advanced solid tumors and lymphomas. Upon completion of the Phase 1 dose escalation study to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several phase Ib/II studies will be implemented accordingly.
- Being tested
- APG-115
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-115Drug
Multiple dose cohorts, PO, every other day of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| APG-115 | Experimental | APG-115 to be explored sequentially during accelerated dose escalation. This will continue until either the occurrence in Cycle 1 of one DLT or two Grade 2 toxicities (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) that are related or possibly related to APG-115. When either of these criteria is fulfilled, dose escalation will be converted to a standard 3+3 escalation scheme, Receives: Drug: APG-115 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Patients with APG-115 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0
Measured: 28 days
Secondary outcomes (3)
Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1
Measured: 18-24 months
Maximum plasma concentration (Cmax) of APG-115 on Day 1-3 and Day 21-23 post APG-115 treatment on cycle 1
Measured: 23 days
Area under the plasma concentration versus time curve (AUC) of APG-115 on Day 1 -3 and Day 21 - 23 post APG-115 treatment on cycle 1
Measured: 23 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2016 (estimated)
- Study startOct 2016
- Primary completion28 Jun 2019
- Study completion28 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Advanced Solid Tumor or LymphomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, MD, PhD, Study chair, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02935907
- Sponsor's protocol ID
- APG-115-US-001
- Acronym
- APG-115
- Status last verified
- Jul 2022
- First submitted
- 13 Oct 2016
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-115 in Patients With Advanced Solid Tumors or Lymphomas
- ClinicalTrials.gov ID
- NCT02935907
- Acronym / sponsor ID
- APG-115 / APG-115-US-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2016 (actual)
- Primary completion
- 28 Jun 2019 (actual)
- Study completion
- 28 Jun 2019 (actual)
- First posted
- 18 Oct 2016 (estimated)
- 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.
APG-115 is a novel, orally active small-molecule mouse double minute 2 homolog (MDM2) inhibitor. Mechanistically, APG-115 increases p53 and p21 overexpression, activates p53 - mediated apoptosis in tumor cells retaining wild-type p53. APG-115 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft and a patient derived xenograft (PDX) models. The preclinical data generated from APG-115 suggest that it may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-115 is intended for the treatment of patients with advanced solid tumors and lymphomas. Upon completion of the Phase 1 dose escalation study to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several phase Ib/II studies will be implemented accordingly.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APG-115 | Experimental | Drug: APG-115APG-115 to be explored sequentially during accelerated dose escalation. This will continue until either the occurrence in Cycle 1 of one DLT or two Grade 2 toxicities (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) that are related or possibly related to APG-115. When either of these criteria is fulfilled, dose escalation will be converted to a standard 3+3 escalation scheme, |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or no standard treatment is available. Only patients with advanced/metastatic cancer who have disease progression after treatment with all available therapies that are known to confer clinical benefit.
- Male or non-pregnant, non-lactating female patients age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- Adequate hematologic and bone marrow functions
- Adequate renal and liver function
Key exclusion criteria (14 listed)
- Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti estrogen analogs, agonists required to suppress serum testosterone levels); or any investigational therapy within 14 days prior to the first dose of study drug.
- Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug.
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 2.
- Has gastrointestinal conditions that could affect the absorption of APG-115 in the opinion of the Investigator.
- Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted.
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-115Multiple dose cohorts, PO, every other day of a 28 day cycle | Drug | APG-115 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 28 days
Patients with APG-115 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0
3 secondary outcomes
Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1
Time frame: 18-24 months
Maximum plasma concentration (Cmax) of APG-115 on Day 1-3 and Day 21-23 post APG-115 treatment on cycle 1
Time frame: 23 days
Area under the plasma concentration versus time curve (AUC) of APG-115 on Day 1 -3 and Day 21 - 23 post APG-115 treatment on cycle 1
Time frame: 23 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Yifan Zhai, MD, PhD study chair
Ascentage Pharma Group Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG-115 in people with Patients With Advanced Solid Tumor or Lymphoma, run by Ascentage Pharma Group Inc. at 2 sites in United States.
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 14 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: finished, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: 28 days). 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 12 Jul 2022.