Clinical Trials /

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

NCT03611868

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: APG-115-US-002
  • NCT ID: NCT03611868

Conditions

  • Unresectable or Metastatic Melanoma or Advanced Solid Tumors

Interventions

DrugSynonymsArms
APG-115+PembrolizumabAPG-115+Pembrolizumab open label, two-part phase Ib/II

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
APG-115+Pembrolizumab open label, two-part phase Ib/IIExperimentalsingle arm dose escalation and dose expansion
  • APG-115+Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        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

        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.

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:21 days
Safety Issue:
Description:Part I is to assess the safety and tolerability of APG-115 by assessing the Dose Limiting Toxicity of APG-115 in combination with pembrolizumab. End points included: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

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