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

  • STATUS
    Recruiting
  • End date
    Oct 31, 2023
  • participants needed
    203
  • sponsor
    Ascentage Pharma Group Inc.
Updated on 13 March 2022
metastatic melanoma
systemic therapy
measurable disease
carcinoma
growth factor
lung adenocarcinoma
pembrolizumab
cancer chemotherapy
alopecia
STK11
LKB1
metastatic urothelial carcinoma
programmed cell death protein 1
mpnst

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 in patients with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) refractory/relapsed melanoma or NSCLC, lung adenocarcinoma with STK11 mutation, solid tumors with P53 WT and ATM mutation, P53 WT and MDM2 amplification liposarcomas, PD-1/PD-L1 refractory/relapsed urothelial carcinoma without FGFR translocation mutation, and MPNST.

Description

Part 1 is the open label, dose-escalation phase Ib portion of the study to establish the maximum tolerated dose (MTD)/RP2D of APG-115 in combination with pembrolizumab. Four dose levels of APG-115 will be administered: 50 mg, 100 mg, 150 mg, and 200 mg. APG-115 will be administered orally every other day (QOD) for consecutive 2 weeks and 1 week off dosing as a cycle of 21 days (3 weeks), pembrolizumab will administrated with label dose.

Part 2 is a phase II study design, includes cohort A-F six arms. The patients will be treated with APG-115 at 150 mg QOD (RP2D) in combination with pembrolizumab until disease progression, unacceptable toxicity, or another discontinuation criterion is met.

Details
Condition Unresectable or Metastatic Melanoma or Advanced Solid Tumors, Melanoma, Uveal Melanoma, Non Small Cell Lung Cancer, ATM Gene Mutation, P53 Mutation, MDM2 Gene Mutation, Liposarcoma, Urothelial Carcinoma, MPNST, Cutaneous Melanoma, Mucosal Melanoma, Malignant Peripheral Nerve Sheath Tumors, STK11 Gene Mutation
Treatment APG-115+Pembrolizumab
Clinical Study IdentifierNCT03611868
SponsorAscentage Pharma Group Inc.
Last Modified on13 March 2022

Eligibility

Yes No Not Sure

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 1
Histologically confirmed, unresectable or metastatic melanoma, or advanced solid tumor patients who failed standard of care therapy and no further effective therapy is available
Eastern Cooperative Oncology Group (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)
Part 2
Cohort B: Histologically confirmed, unresectable or metastatic NSCLC, and refractory or relapse after PD-1/PD-L1 antibody treatment and ineligible for other standard of care therapy per NCCN guideline or Histologically confirmed, unresectable or metastatic lung adenocarcinoma with STK-11 mutation, and with or without previous anti-PD-1/PD-L1 antibody treatment and ineligible for other standard of care therapy per NCCN guideline
Cohort C: Histologically confirmed, unresectable or metastatic solid tumors with P53WT and ATM mutation (including germline ATM mutation)
Cohort D: Histologically confirmed, locally advanced or metastatic well-differentiated or dedifferentiated liposarcomas who have or haven't received prior systemic therapy (either ineligible or declining chemotherapy), and with P53 WT and MDM2 amplification
Cohort E: Histologically confirmed, unresectable or metastatic urothelial carcinoma, and refractory or relapse after PD-1/PD-L1 antibody treatment and ineligible for other standard of care therapy per NCCN guideline
Cohort F: Histologically confirmed, metastatic or unresectable MPNST
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
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 two 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

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 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 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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note