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NCT03611868 | RECRUITING | Unresectable or Metastatic Melanoma or Advanced Solid Tumors

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

Ascentage Pharma Group Inc.

Brief 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. 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.

Condition or disease

Unresectable or Metastatic Melanoma or Advanced Solid Tumors

Melanoma

Uveal Melanoma

P53 Mutation

MDM2 Gene Mutation

Cutaneous Melanoma

Mucosal Melanoma

Malignant Peripheral Nerve Sheath Tumors (MPNST)

Intervention/treatment

Phase 1b: APG-115+pembrolizumab

Phase

PHASE1

PHASE2

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).

Study Type : INTERVENTIONAL
Estimated Enrollment : 230 participants
Masking : NONE
Primary Purpose : TREATMENT
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
Actual Study Start Date : 2018-08-29
Estimated Primary Completion Date : 2024-12-30
Estimated Study Completion Date : 2025-03-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 12 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • * 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
    • 1. 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
    • 2. ECOG performance status 0-2
    • 3. 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)
    • 4. Cohort F: Histologically confirmed, metastatic or unresectable MPNST
    • * 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.
    Exclusion Criteria
    • * 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
    • * 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.
A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

Location Details

NCT03611868

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Arizona

University of Arizona Cancer Center

Tucson, Arizona, United States, 85724

RECRUITING

United States, Arkansa

Highlands Oncology

Rogers, Arkansa, United States, 72758

RECRUITING

United States, California

UCLA Hematology & Oncology Clinic

Los Angeles, California, United States, 90095

RECRUITING

United States, California

Sarcoma Oncology Research Center

Santa Monica, California, United States, 90403

RECRUITING

United States, District of Columbia

Children's National Research Institute

Washington, District of Columbia, United States, 20010

RECRUITING

United States, Florida

Sarah Cannon/FCSRI

Fort Myers, Florida, United States, 33908

RECRUITING

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

ACTIVE NOT RECRUITING

United States, New York

Memorial Sloan Kettering

New York, New York, United States, 10065

ACTIVE NOT RECRUITING

United States, North Carolina

Duke Cancer Institute

Durham, North Carolina, United States, 27710

RECRUITING

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

RECRUITING

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

RECRUITING

United States, Pennsylvania

Penn State Hershey Medical Center Cancer Institute

Hershey, Pennsylvania, United States, 17033

ACTIVE NOT RECRUITING

United States, Pennsylvania

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

ACTIVE NOT RECRUITING

United States, Tennessee

Sarah Cannon Cancer Center

Nashville, Tennessee, United States, 37203

RECRUITING

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

RECRUITING

United States, Texas

Next Oncology

San Antonio, Texas, United States, 78229

RECRUITING

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

ACTIVE NOT RECRUITING

Australia, Queensland

Metro South Hospital and Health Services via Princess Alexandra Hospital

Brisbane, Queensland, Australia,

ACTIVE NOT RECRUITING

Australia, Queensland

Queensland Children's Hospital

South Brisbane, Queensland, Australia, 4101

ACTIVE NOT RECRUITING

Australia, South Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia, 5042

ACTIVE NOT RECRUITING

Australia, Victoria

Austin Health

Heidelberg, Victoria, Australia,