A Clinical Study of TJ004309 With Atezolizumab (TECENTRIQ®) in Patients With Ovarian Cancer and Selected Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab in patients with advanced or metastatic solid tumors.

Detailed Description
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This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab in patients with advanced or metastatic solid tumors. This clinical study includes two cohorts: Cohort 1 will include Immuno-Oncology (IO) treatment naïve ovarian cancer (OC) patients who have progressed on or after platinum therapy; and Cohort 2 will include patients with head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), gastrointestinal cancer (GC), triple negative breast cancer (TNBC), or ovarian carcinoma (OC) with PD-L1 expression ≥ 1%. Additional cohorts for selected tumor types might be added later.

Official Title
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A Phase 2 Clinical Study of TJ004309 in Combination With Atezolizumab (TECENTRIQ®) in Patients With Advanced or Metastatic Ovarian Cancers and Selected Advanced Solid Tumors

Conditions
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Ovarian Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Gastrointestinal Cancer, Triple Negative Breast Cancer, Ovarian Carcinoma

Intervention / Treatment
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* Drug: TJ004309


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Patients with histologically confirmed epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer subjects with any high-grade serous component, progressed on or after platinum-containing therapy and not eligible for further platinum containing treatment (platinum-resistant, platinum-refractory disease defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of receiving the last dose of platinum-based treatment). Cohort 2: Patients with selected tumor types that have relapsed or progressed after 2 lines of therapy or who are ineligible for other standard of care (SOC) therapies: Histologically or cytologically confirmed metastatic NSCLC Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, hypopharynx, or larynx) Histologically or cytologically confirmed metastatic or non-resectable advanced metastatic gastric or gastroesophageal adenocarcinoma Histologically or cytologically confirmed unresectable, locally advanced or metastatic TNBC (confirmed HER2-negative, estrogen receptor-negative and progesterone receptor-negative) Histologically confirmed ovarian cancer of all high-grade epithelial types who are IO treatment naïve and have progressed after 3 months on or after platinum-containing therapy PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% for NSCLC and Combined Proportion Score (CPS) ≥ 1% for all other tumor types A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1 therapy Patients should have no more than 5 prior lines of therapies Cohort 2 - (Optional for the ovarian cohort) Pre-treatment fresh tumor biopsies and paired treatment fresh tumor biopsies will be collected from at least 5 patients. Biopsy must be excisional, incisional, or core. Exclusion Criteria: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40 [Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) (only applies to ovarian cancer patients in Cohorts 1 and 2) Disease progression within 6 months of starting anti-PD-1 and anti-PD-L1 inhibitors Known active or chronic Hepatitis B or Hepatitis C, other hepatitides (non-alcohol steatohepatitis, alcohol or drug-related, autoimmune) serology at screening or cirrhosis Active autoimmune disease requiring systemic treatment within the past 12 months Active interstitial lung disease (ILD) or pneumonitis or a history of ILD Brain involvement with cancer, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease; unless the lesion(s) have been radiated or resected, are considered fully treated and inactive, are asymptomatic, and no steroids have been administered for CNS disease over the 7 days prior to study treatment Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment Known human immunodeficiency virus (HIV) unless CD4+ T cell count > 350 cells/μL with an undetectable viral load

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TJ004309 and Atezolizumab<br>TJ004309 20 mg/kg Q3W in combination with atezolizumab 1200 mg Q3W | Drug: TJ004309<br>* Antibody to CD73<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) in each Tumor Type | Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumors (RECIST v1.1) and iRECIST for target lesions assessed by CT or MRI | Up to 120 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | Treatment-emergent adverse event (TEAE) is assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0) Number of subjects with significant changes in vital signs, physical examinations, and clinical laboratory findings | Up to 120 weeks | 
| Number of participants with laboratory value abnormalities | Assessed by number of participants with clinically significant laboratory values. | Up to 120 weeks | 
| Number of participants with vital sign abnormalities | Assessed by number of participants with clinically significant vital sign values | Up to 120 weeks | 
| Number of participants with abnormal physical examination results | Assessed by number of participants with clinically significant abnormal physical examination results | Up to 120 weeks | 
| Objective Response Rate (ORR) | Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumors (RECIST v1.1) and iRECIST for target lesions assessed by CT or MRI | Up to 120 weeks | 
| Duration of response (DOR) | Time from documentation of tumor response to disease progression assessed among patients who had an objective response | Up to 120 weeks | 
| Disease control rate (DCR) | Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1 | Up to 120 weeks | 
| Progression-free-survival (PFS) | by RECIST v1.1 and iRECIST | Up to 120 weeks | 
| Overall survival (OS) | Overall survival (OS) will be calculated for each subject as the number of days from the first day of treatment (Cycle 1 Day 1) to the date of death from any cause. | Up to 120 weeks | 
| Pharmacokinetic profiles of serum TJ004309 and atezolizumab | Based on Anti-Drug Antibody Results | Up to 120 weeks | 
| Pharmacokinetic (PK) parameters: Area under the curve (AUC0-T) | AUC0-T is the area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval after the first infusion | From pre-dose in Day 1 of Cycle 1 to post-dose in Day 21 of Cycle 1 (each cycle is 21 days) | 
| Assessment of PK parameter: Cmax | Cmax is maximum drug concentration observed | From pre-dose in Day 1 of Cycle 1 to post-dose in Day 21 of Cycle 1 (each cycle is 21 days) | 
| Assessment of PK parameter: tmax | Time to reach Cmax | From pre-dose in Day 1 of Cycle 1 to post-dose in Day 21 of Cycle 1 (each cycle is 21 days) |