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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||June 2020||Phase 1||Interventional|
Primary Outcome 1 - Measure: Primary Outcome Measure
Primary Outcome 1 - Time Frame: 3 weeks
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Diagnosed with histologically confirmed locally advanced and nonresectable, or metastatic
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.
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.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Jin Jin, Ph.D.
Role: Study Director
Affiliation: ADLAI NORTYE USA INC.