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Advanced Solid Tumors or Hematologic MalignanciesPhase 1NCT03386526

APG-1387 in Patients With Advanced Solid Tumors or Hematologic Malignancies

A Phase 1 study testing APG-1387 for Injection in people with Advanced Solid Tumors or Hematologic Malignancies, run by Ascentage Pharma Group Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

APG-1387 is a potent, bivalent small-molecule Inhibitor of Apoptosis Protein (IAP) antagonist. APG-1387 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft models, APG-1387 also demonstrates its synergistic effect in combination with immune checkpoint inhibitor… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APG-1387 for Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
3 sitesUnited States
Study dates
21 Nov 2017to 30 Nov 2022
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 solid tumor or hematological malignancies
  • Life expectancy ≥ 3 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  • Corrected QT interval (QTc) ≤ 450 ms in males, and ≤ 470 ms in females
  • Adequate hematologic function
  • International normalized ratio (INR), prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x upper limit of normal (ULN)
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  • Adequate renal and liver function
  • Willingness to use contraception
  • Ability to understand and willingness to sign a written informed consent form
  • Willingness and ability to comply with study procedures and follow-up examination
  • Have provided tissue for biomarker analysis from a newly or recently-obtained biopsy of a tumor lesion not previously irradiated

Who cannot join

  • Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to entering the study
  • Received hormonal, biologic (< 2 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days of study entry
  • Radiation or surgery within 14 days of study entry, thoracic radiation within 28 days of study entry
  • Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Patients who have received prior radiotherapy for previous brain metastasis must have discontinued steroids for 14 days prior to study entry and be clinically stable
  • Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia
  • Requirement for corticosteroid treatment, with the exception of megestrol, local use of steroid
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  • Use of therapeutic anticoagulants
  • International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≥ 1.5 x ULN
  • Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy
  • 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)
  • History of Bell's palsy
  • Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation
  • Active infection requiring systemic antibiotic/ antifungal medication
  • Known or suspected Wilson's Disease
  • Prior treatment with IAP inhibitors
  • History of hypersensitivity to paclitaxel, or any therapeutic antibody
  • Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
  • Is on chronic systemic steroid therapy
  • Has received a live vaccine within 30 days prior to first dose
  • Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • START Midwest

    Grand Rapids, Michigan, 49503

  • The START Center for Cancer Care

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase I Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 as a Single Agent or in Combination With Systemic Anti-Cancer Agents in Patients With Advanced Solid Tumors or Hematologic Malignancies

APG-1387 is a potent, bivalent small-molecule Inhibitor of Apoptosis Protein (IAP) antagonist. APG-1387 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft models, APG-1387 also demonstrates its synergistic effect in combination with immune checkpoint inhibitor anti-PD-1 antibody, and such a combinatory effect was further enhanced by chemotherapeutic agent. A total of 35 patients with advanced solid tumors or lymphomas have been treated with APG-1387 in two Phase I dose-escalation studies in Australia and in China. Ten dose levels have been tested ranging from 0.3 mg to 45 mg in these two studies. Based on the preliminary results, APG-1387 is well-tolerated at the dose levels evaluated to date. APG-1387 is intended for the treatment of patients with advanced solid tumors and hematologic malignancies. After establishing the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several Ib /II studies will be implemented accordingly to further access the antitumor effects of APG-1387 in combination with either pembrolizumab or the chemotherapeutic agents.

Being tested
APG-1387 for Injection
Keywords
IAP inhibitor
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APG-1387 for InjectionDrug

    Multiple dose cohorts, 30 minute IV infusion, once weekly for 3 weeks of a 21-day cycle

Study groups in NCT03386526
Study groupRoleWhat they receive
APG-1387 for InjectionExperimentalAPG-1387 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase and up to 20 patient per group at the dose expansion phase.
Receives: Drug: APG-1387 for Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.03

    Measured: 18-24 months

Secondary outcomes (5)

  1. Anti-tumor effects of APG-1387 as a single agent

    Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1 or the Revised Response Criteria for Malignant Lymphoma

    Measured: 18-24 months

  2. Pharmacokinetic evaluation

    Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-1387

    Measured: 18-24 months

  3. Anti-tumor effects of APG-1387 in combination with pembrolizumab or combination with paclitaxel and carboplatin in patients with advanced solid tumors

    Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1 or the Revised Response Criteria for Malignant Lymphoma

    Measured: 18-24 months

  4. Preliminary biomarker assessment

    Tumor biopsy and peripheral blood sample at baseline and 15-21 days after administration of APG-1387 alone or in combination with systemic anti-cancer therapy

    Measured: 18-24 months

  5. Pharmacokinetic evaluation

    Area under the plasma concentration versus time curve (AUC) of APG-1387 will be assessed on patients treated with APG-1387

    Measured: 18-24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2017
  2. Study start21 Nov 2017
  3. Primary completion31 Oct 2022
  4. Study completion30 Nov 2022

Resources

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
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03386526
Sponsor's protocol ID
APG-1387-US-001
Status last verified
Jan 2023
First submitted
13 Dec 2017
Last updated
1 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pan W, Luo Q, Liang E, Shi M, Sun J, Shen H, Lu Z, Zhang L, Yan X, Yuan L, Zhou S, Yi H, Zhai Y, Qiu MZ, Yang D. Synergistic effects of Smac mimetic APG-1387 with anti-PD-1 antibody are attributed to increased CD3 + NK1.1 + cell recruitment secondary to induction of cytokines from tumor cells. Cancer Cell Int. 2024 May 24;24(1):181. doi: 10.1186/s12935-024-03373-7.

    PubMed 38790057

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing APG-1387 for Injection in people with Advanced Solid Tumors or Hematologic Malignancies, run by Ascentage Pharma Group Inc. at 3 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 11 inclusion and 21 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 1 Feb 2023. 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 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: 18-24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03386526, which also lists 1 linked publication.

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 1 Feb 2023.

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