Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03611868




Registration number
NCT03611868
Ethics application status
Date submitted
27/07/2018
Date registered
2/08/2018
Date last updated
1/02/2024

Titles & IDs
Public title
A Study of APG-115 in Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors
Scientific title
A Phase Ib/II Study of APG-115 in Combination With Pembrolizumab in Patients With Unresectable or Metastatic Melanomas or Advanced Solid Tumors
Secondary ID [1] 0 0
Keynote MK-3475-B66
Secondary ID [2] 0 0
APG-115-US-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Melanoma or Advanced Solid Tumors 0 0
Melanoma 0 0
Uveal Melanoma 0 0
P53 Mutation 0 0
MDM2 Gene Mutation 0 0
MPNST 0 0
Cutaneous Melanoma 0 0
Mucosal Melanoma 0 0
Malignant Peripheral Nerve Sheath Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APG-115+Pembrolizumab

Experimental: APG-115+Pembrolizumab open label, two-part phase Ib/II - single arm dose escalation and dose expansion


Treatment: Drugs: APG-115+Pembrolizumab
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 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 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Recommended Phase II Dose
Timepoint [2] 0 0
21 days
Primary outcome [3] 0 0
Overall Response Rate
Timepoint [3] 0 0
up to 12 months

Eligibility
Key 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 as indicated by the following laboratory
values without continuous supportive treatment (such as blood transfusion, coagulation
factors and/or platelet infusion, red/white blood cell growth factor administration,
or albumin infusion) as assessed by laboratory for eligibility

- 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 the
investigator by both male and female patients of child bearing potential
(postmenopausal women must have been amenorrhea 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 screening procedures).
Willingness and ability to comply with study procedures and follow-up examination.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

- Uncontrolled concurrent illness including, but not limited to: symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with the study requirements

- Has an active autoimmune disease, or a documented history of autoimmune disease, or a
syndrome, that requires systemic steroids or immunosuppressive agents. Subjects with
vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
Subjects that require intermittent use of bronchodilators or local steroid injections
are not excluded from the study. Subjects with hypothyroidism stable on hormone
replacement are not excluded from the study.

- Has received a live vaccine within 30 days prior to first dose. Note that killed
vaccines, mRNA vaccines, and non-live attenuated vaccines (i.e., for the SARS-Cov-2
virus or COVID-19) are allowed for patients on study.

- Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow
transplant

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis

- 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. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/03/2025
Actual
Sample size
Target
224
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Metro South Hospital and Health Services via Princess Alexandra Hospital - Brisbane
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ascentage Pharma Group Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Part 1 is the dose escalation of APG-115 in combination with label dose of pembrolizumab.

Part 2 is phase II design of APG-115 at recommended phase 2 dose (RP2D) in combination with
pembrolizumab.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03611868
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yifan Zhai, MD, PhD
Address 0 0
Ascentage Pharma Group Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Angela Kaiser
Address 0 0
Country 0 0
Phone 0 0
301-509-0357
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03611868