Clinical Trials /

AN0025 and Pembrolizumab Combination in Advanced Solid Tumors

NCT04432857

Description:

This is an open-label, multicenter, phase Ib study to evaluate the safety and preliminary efficacy of AN0025 in combination with pembrolizumab in patients with locally advanced/metastatic tumors. It will include a dose-limiting toxicity observation phase followed by an expansion phase. All enrolled patients will be treated with AN0025 and Pembrolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles (approximately 2 years). The dose of pembrolizumab will remain constant at 200 mg every 3 weeks (Q3W) for each dose level of AN0025 and in each cohort.

Related Conditions:
  • Bladder Urothelial Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AN0025 and Pembrolizumab Combination in Advanced Solid Tumors
  • Official Title: An Open-Label Multicenter Phase Ib Study of AN0025 in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: AN0025S0103
  • SECONDARY ID: 2019-003960-37
  • SECONDARY ID: Keynote 879
  • NCT ID: NCT04432857

Conditions

  • Triple-negative Breast Cancer
  • NSCLC, Squamous or Non-Squamous
  • Urothelial Carcinoma of the Bladder
  • Microsatellite Stable (MSS) Colorectal Cancer (CRC)
  • Cervical Cancer

Interventions

DrugSynonymsArms
AN0025E7046Ph1a: Urothelial carcinoma of the bladder and NSCLC
PembrolizumabKeytruda, MK3475-879Ph1a: Urothelial carcinoma of the bladder and NSCLC

Purpose

This is an open-label, multicenter, phase Ib study to evaluate the safety and preliminary efficacy of AN0025 in combination with pembrolizumab in patients with locally advanced/metastatic tumors. It will include a dose-limiting toxicity observation phase followed by an expansion phase. All enrolled patients will be treated with AN0025 and Pembrolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles (approximately 2 years). The dose of pembrolizumab will remain constant at 200 mg every 3 weeks (Q3W) for each dose level of AN0025 and in each cohort.

Trial Arms

NameTypeDescriptionInterventions
Ph1a: Urothelial carcinoma of the bladder and NSCLCExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab
Phase 1b: Urothelial carcinoma of the bladderExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab
Phase 1b: Non-Small Cell Lung Cancer (NSCLC)ExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab
Phase 1b: Triple-negative breast cancer (TNBC)ExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab
Phase 1b: CervicalExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab
Phase 1b: Microsatellite Stable (MSS) Colorectal Cancer (CRC)ExperimentalPatients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.
  • AN0025
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

        Diagnosed with histologically confirmed locally advanced and nonresectable, or metastatic
        disease.

        Phase 1a:

        Patients with urothelial carcinoma of the bladder, or squamous or non-Squamous NSCLC

        Phase 1b Expansion Cohort:

        Patients diagnosed with one of the following tumor types:

        A. Urothelial carcinoma of the bladder B. NSCLC, Squamous or Non-Squamous C. TNBC D.
        Cervical cancer E. MSS CRC

        Have progressed on treatment with an anti-PD-1/PD-L1monoclonal antibody (mAb) administered
        either as monotherapy, or in combination with other checkpoint inhibitors or other
        therapies (phase 1a, phase 1b cohort A or B) or with no prior anti-PD-1/PD-L1 therapy and
        failed standard of care treatment (phase 1b cohort C, D, or E).

        Have received no more than 3 prior lines of systemic therapy for advanced disease.

        Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a
        tumor lesion not previously irradiated.

        Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple
        gated acquisition (MUGA) scan.

        Have adequate organ function.

        Exclusion Criteria:

        Have been discontinued treatment due to a Grade 3 or higher immune-related (irAE) from
        prior anti-PD-1or anti-PD-L1, or with an agent directed to another stimulatory or
        co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)

        Have received prior systemic anti-cancer therapy including investigational agents within 4
        weeks or 5 half-lives, whichever is shorter prior to treatment.

        Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
        dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
        immunosuppressive therapy within 7 days prior to the first dose of study drug.

        With a history of another primary malignancy within the past 2 years, with the exception of
        basal or squamous cell skin cancer, or carcinoma in situ of the cervix or breast that has
        undergone potentially curative therapy.

        Have known active CNS metastases and/or carcinomatous meningitis.

        Participants with known human immunodeficiency virus (HIV) and/or history of Hepatitis B or
        C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus
        (HBV) DNA or Hepatitis C Antibody or RNA.

        Prolongation of corrected QT.

        Significant cardiovascular impairment.

        Inability to take oral medication, or malabsorption syndrome or any other uncontrolled
        gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the
        bioavailability of AN0025.

        Is pregnant or breastfeeding or expecting to conceive or father children within the
        projected duration of the study, starting with the screening visit through 120 days after
        the last dose of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Outcome Measure
Time Frame:3 weeks
Safety Issue:
Description:Number of participants with Dose Limiting Toxicities (DLTs)

Secondary Outcome Measures

Measure:ORR and Progression-Free Survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame:2 years
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Efficacy by PD-L1 expression
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Adlai Nortye Biopharma Co., Ltd.

Last Updated

June 26, 2020