Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

Summary

Part 1 is a phase Ib standard "3 + 3" design will be employed to determine the MTD of APG-115 by assessing the DLT of APG-115 in combination with pembrolizumab. Part 2 is a Simon two-stage phase II study design. At RP2D of APG-115 in combination with pembrolizumab, approximately 43 patients will be treated with the combination until disease progression, unacceptable toxicity, or another discontinuation criterion is met.

Official Title

A Phase Ib/II Study of APG-115 in Combination With Pembrolizumab in Patients With Unresectable or Metastatic Melanomas or Advanced Solid Tumors

Details

Part 1 is the open label, dose-escalation phase Ib portion of the study to establish an MTD/RP2D of APG-115 in combination with pembrolizumab. Dose levels/schedule of APG115 will be tested: 50mg, 100mg, 150mg, and 200mg, QOD with 2 weeks on 1 week off as a cycle of 21 days (3 weeks), pembrolizumab will administrated with label dose.

Part 2 is the phase II portion of the study to evaluate the clinical efficacy and safety of the RP2D of APG-115 in combination with label dose of pembrolizumab in patient with unresectable or metastatic melanoma who is refractory or relapse of PD1 therapy. In this part, Simon's two-stage design (Simon R (1989). Controlled Clinical Trials 10: 1-10.) will be used. The null hypothesis that the true response rate is 10% or lower will be tested against a one-sided alternative. In the first stage, 18 patients will be accrued. If there are 2 or fewer responses in these patients, the study will be stopped. Otherwise, 25 additional patients will be accrued for a total of 43. The null hypothesis will be rejected if 8 or more responses are observed in 43 patients. This design yields a type I error rate of 0.10 and power of 80% when the true response rate is 25% or higher.

Keywords

Unresectable or Metastatic Melanoma or Advanced Solid Tumors Melanoma Pembrolizumab APG-115+Pembrolizumab

Eligibility

You can join if…

Open to people ages 18 years and up

Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent

Part 1:

  1. Histologically confirmed, unresectable or metastatic melanoma or advanced solid tumor patients who failed standard of care therapy;
  2. ECOG PS 0-2
  3. No CNS metastases

Part 2:

  1. Histologically confirmed, unresectable or metastatic melanoma, and refractory or relapse after PD1 antibody treatment and ineligible for other standard of care therapy;
  2. ECOG PS 0-2;
  3. Measurable disease according to irRECIST and 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 Life expectancy ≥ 3 months Continuance of treatment related toxicities (except alopecia) due to prior radiotherapy or chemotherapy agents or biological therapy (including PD1/PDL1 antibodies) must ≤ 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 QTc interval (mean of 3) ≤450ms in males, and ≤470ms in females Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

You CAN'T join if...

Any prior systemic MDM2-p53 inhibitor treatment Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to first dose.

Prior loco-regional treatment with intralesional therapy (e.g. talimogene laherparepvec) for unresectable or metastatic melanoma in the last 6 months prior to start of study treatment.

Received hormonal and biologic (<1 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days prior to first dose Radiation or surgery within 14 days of study entry, 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, 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 28 days prior to the first dose of therapy

Locations

  • UCLA not yet accepting patients
    Los Angeles California 90095 United States
  • University of Arizona Cancer Center accepting new patients
    Tucson Arizona 85724 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ascentage Pharma Group Inc.
ID
NCT03611868
Phase
Phase 1/2
Study Type
Interventional
Last Updated