AN0025 and Pembrolizumab Combination in Advanced Solid Tumors

Overview

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.

Full Title of Study: “An Open-Label Multicenter Phase Ib Study of AN0025 in Combination With Pembrolizumab in Patients With Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2022

Interventions

  • Drug: AN0025
    • oral administration
  • Drug: Pembrolizumab
    • Infusion

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Adlai Nortye Biopharma Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jin Jin, Ph.D., Study Director, ADLAI NORTYE USA INC.
  • Overall Contact(s)
    • Nathan Lautermilch, Ph.D., 1-848-230-7430, Nathan.Lautermilch@adlainortye.com

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