ACTIVE_NOT_RECRUITING

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

Conditions

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)Metastatic melanoma, MPNST and Advanced Solid Tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2018-08-29

Study Completion:2025-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT03611868

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Principal Investigator

Yifan Zhai, MD, PhD

STUDY_CHAIR

Ascentage Pharma

Study Locations (Sites)

University of Arizona Cancer Center

Tucson, Arizona, 85724

United States

Highlands Oncology

Rogers, Arkansas, 72758

United States

UCLA Hematology & Oncology Clinic

Los Angeles, California, 90095

United States

Sarcoma Oncology Research Center

Santa Monica, California, 90403

United States

Children's National Research Institute

Washington, District of Columbia, 20010

United States

Sarah Cannon/FCSRI

Fort Myers, Florida, 33908

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Memorial Sloan Kettering

New York, New York, 10065

United States

Duke Cancer Institute

Durham, North Carolina, 27710

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Penn State Hershey Medical Center Cancer Institute

Hershey, Pennsylvania, 17033

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107

United States

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203

United States

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Next Oncology

San Antonio, Texas, 78229

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Ascentage Pharma Group Inc.

Yifan Zhai, MD, PhD, STUDY_CHAIR, Ascentage Pharma

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-08-29

Study Completion Date2025-12-30

Study Record Updates

Study Start Date2018-08-29

Study Completion Date2025-12-30

Terms related to this study

Keywords Provided by Researchers

Metastatic melanoma, MPNST and Advanced Solid Tumors

Additional Relevant MeSH Terms

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)