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Unresectable or Metastatic Melanoma or Advanced Solid TumorsPhase 1/2NCT03611868

A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

A Phase 1/2 study testing Phase 1b: APG-115+pembrolizumab in people with Unresectable or Metastatic Melanoma or Advanced Solid Tumors and Melanoma, run by Ascentage Pharma Group Inc. at 21 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study aims to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of APG-115, an MDM2 inhibitor, either alone or in combination with pembrolizumab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with metastatic melanomas or advanced solid tumors. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Phase 1b: APG-115+pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
230 participants
Where
21 sitesin 2 countries
Study dates
29 Aug 2018to 30 Dec 2025
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or non-pregnant, non-lactating female patients age ≥18 years, an exception for MPNST cohort: adolescents ≥12 years old (who weigh at least 40 kg) is allowed
  • Part 2:
  • Measurable disease according to RECIST 1.1. Lesions situated in a previously irradiated area, or an area subject to other loco-regional therapy (e.g., intralesional injections) should be considered non-measurable
  • ECOG performance status 0-2
  • Cohort A: Histologically confirmed, unresectable or metastatic melanoma, and refractory or relapse after PD-1 antibody treatment and ineligible for other standard of care therapy per NCCN guideline (previous PD-1/PD-L1 antibody treatment not required for uveal melanoma)
  • Cohort F: Histologically confirmed, metastatic or unresectable MPNST
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  • Life expectancy ≥ 3 months
  • Continuance of treatment related toxicities (except alopecia) due to prior radiotherapy or chemotherapy agents or biological therapy (including PD-1/PD-L1 antibodies) must be ≤ grade 1 at the time of dosing
  • Adequate bone marrow and organ function without continuous supportive treatment
  • QTcF interval (mean of 3, 1-3 minutes between tests) ≤450 ms in males and ≤470 ms in females
  • Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  • Tumor tissue must be provided for all subjects for biomarker analysis before treatment with investigational product
  • Willingness to use contraception by a method that is deemed effective by both male and female patients of 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.

Who cannot join

  • Any prior systemic MDM2-p53 inhibitor treatment
  • Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to first dose
  • Part 2 Cohort A: Prior loco-regional treatment with intralesional therapy (e.g., talimogene laherparepvec) for unresectable or metastatic melanoma in the last 6 weeks prior to start of study treatment
  • Part 2 Cohort B: Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment
  • Part 2 Cohort E: Known FGFR translocation mutation
  • Received hormonal and biologic, small molecule targeted therapies or other anti-cancer therapy within 21 days prior to first dose
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  • Radiation or surgery within 14 days prior to first dose, thoracic radiation within 28 days prior to first dose
  • Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Or has neurologic instability per clinical evaluation due to tumor involvement of the CNS.
  • Requirement for corticosteroid treatment (with the exception of megestrol and local use of steroid: i.e., topical corticosteroids, inhaled corticosteroids for reactive airway disease, ophthalmic, intraarticular, and intranasal steroids
  • Concurrent treatment with an investigational agent or device within 21 days prior to the first dose of therapy
  • Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from 1st dose of study treatment, and patients who have had minor surgery within 14 days from 1st dose of study treatment.
  • Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
  • 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, and known clinically active viral infection such as hepatitis B or C, HIV infection, or active COVID-19
  • 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
  • Has previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
  • Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
  • History of organ transplant requiring use of immunosuppressive medication
  • A woman of childbearing potential who has a positive urine or serum pregnancy test (within 72 hours) prior to treatment.

Trial locations and contacts

21 sites in 2 countries.

21 sites in 2 countries

United States17 sites

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Sarah Cannon/FCSRI

    Fort Myers, Florida, 33908

  • Penn State Hershey Medical Center Cancer Institute

    Hershey, Pennsylvania, 17033

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCLA Hematology & Oncology Clinic

    Los Angeles, California, 90095

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering

    New York, New York, 10065

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Highlands Oncology

    Rogers, Arkansas, 72758

  • Next Oncology

    San Antonio, Texas, 78229

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • Children's National Research Institute

    Washington D.C., District of Columbia, 20010

Other trials in United States

Australia4 sites

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Metro South Hospital and Health Services via Princess Alexandra Hospital

    Brisbane, Queensland

  • Austin Health

    Heidelberg, Victoria

  • Queensland Children's Hospital

    South Brisbane, Queensland, 4101

Other trials in Australia

About this study

Official title: A Phase Ib/II Study of APG-115 as a Monotherapy or in Combination With Pembrolizumab in Patients With Unresectable or Metastatic Melanomas or Advanced Solid Tumors

This study aims to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of APG-115, an MDM2 inhibitor, either alone or in combination with pembrolizumab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with metastatic melanomas or advanced solid tumors. Our hypothesis is that restoration of the immune response concomitant to inhibition of the MDM2 pathway (which restores p53 functions) may promote cancer cell death, leading to effective anticancer therapy.

Read the detailed description

This is a phase I/II study to assess the safety and tolerability of APG-115 alone or in combination with pembrolizumab in patients with unresectable or metastatic melanoma, NSCLC, solid tumors with ATM mutation, liposarcoma, urothelial carcinomas, and malignant peripheral nerve sheath tumors (MPNST)The hypothesis is that the current therapy may improve ORR, progression-free survival, and synergistic effect of APG-115 alone or in combination with pembrolizumab in these patients. (n=230, ID: NCT03611868).

Being tested
Phase 1b: APG-115+pembrolizumab
Keywords
Metastatic melanoma, MPNST and Advanced Solid Tumors
Medical subject headings
Melanoma, Uveal Melanoma, Neurofibrosarcoma

What participants receive

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

  • Phase 1b: APG-115+pembrolizumabDrug

    Also called KEYTRUDA®

    dose escalation of APG-115 in combination with label dose of pembrolizumab, Four dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. APG-115 will be administrateddose escalation of APG-115 in combination with label dose of pembrolizumab, Fourfour dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. 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 there are cycles every 3-weeks a cycle. Pembrolizumab is administrated following FDA approved label dose, i.e., 200 mg intravenous infusion at Day 1 of every 3 weeks as a cycle.

    Phase II: Combination of APG-115 at 150 mg (RP2D) and pembrolizumab or APG-115 monotherapy alone.

Study groups in NCT03611868
Study groupRoleWhat they receive
APG-115+pembrolizumab open label, two-part phase Ib/IIExperimentalsingle arm dose escalation and dose expansion
Receives: Drug: Phase 1b: APG-115+pembrolizumab

What is being measured

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

  1. Maximum Tolerated Dose

    Part I is to assess the safety and tolerability of APG-115 by assessing the dose-limiting toxicity (DLT) of APG-115 in combination with pembrolizumab. End points included: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0

    Measured: 21 days

  2. Recommended Phase II Dose

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

    Measured: 21 days

  3. Overall Response Rate

    Phase II is to assess overall response rate of APG-115 as monotherapy and in combination with pembrolizumab defined as the percentage of subjects with a best overall confirmed complete response (CR) or a partial response (PR) at any time as per RECIST 1.1

    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.

  1. First posted2 Aug 2018
  2. Study start29 Aug 2018
  3. Primary completion30 Dec 2025 (estimated)
  4. Study completion30 Dec 2025 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
230 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03611868
Sponsor's protocol ID
APG-115-US-002
Other IDs
Keynote B66, MK3475-B66
Status last verified
Aug 2025
First submitted
27 Jul 2018
Last updated
7 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Phase 1b: APG-115+pembrolizumab in people with Unresectable or Metastatic Melanoma or Advanced Solid Tumors and Melanoma, run by Ascentage Pharma Group Inc. at 21 sites in 2 countries.

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 14 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia. 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?

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 (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?

On the ClinicalTrials.gov record for NCT03611868.

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 7 Aug 2025.

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