A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas

Study Overview
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Brief Summary
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CA-170 is a rationally designed and orally available, small molecule that directly targets the Programmed death-ligands 1 and 2 (PD-L1/PD-L2), and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints and results in activation of T cell proliferation and cytokine production. This is a multi-center, open-label, Phase 1 trial of orally administered CA-170 in adult patients with advanced solid tumors or lymphomas who have progressed or are non-responsive to available therapies and for which no standard therapy exists.

Official Title
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A Phase 1, Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered CA-170 in Patients With Advanced Tumors and Lymphomas

Conditions
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Advanced Solid Tumors or Lymphomas

Intervention / Treatment
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* Drug: CA-170


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age; Life expectancy of at least 3 months; ECOG PS ≤ 1; Acceptable bone marrow and organ function at screening; Ability to swallow and retain oral medications; Negative serum pregnancy test in women of childbearing potential; Measurable disease; Tumor for which standard therapy, including approved anti-PD-1 or anti-PD-L1 therapy, when applicable, does not exist or is no longer effective. For patients enrolling into backfill of dose levels at or below the MTD/RP2D, patients with tumor types known to have a high VISTA expression (such as metastatic malignant pleural mesothelioma of epithelioid histology). Exclusion Criteria: Prior treatment anti-cancer therapy or use of any investigational agent within the past 28 days or 5 half-lives, whichever is shorter; Toxicity from prior chemotherapy that has not resolved to Grade ≤ 1; Radiotherapy within the last 21 days; Primary brain tumors or CNS metastases; Major or minor surgery < 28 and <14 days from the start of treatment, respectively; Active autoimmune disease or any medical condition requiring the use of systemic immunosuppressive medications; Endocrinopathies, unless on stable hormone replacement therapy; Active infection requiring systemic therapy; Receipt of live vaccines against infectious diseases within 28 days; HIV positive or an AIDS-related illness; Active/chronic HBV or HCV infection; Uncontrolled CHF (NYHA Class 2-4), angina, MI, CVA, coronary/peripheral artery bypass graft surgery, TIA, or PE in prior 3 months; Cardiac dysrhythmias; Gastrointestinal disease that interferes with receipt of oral drugs; Concomitant malignancy; Pregnant or lactating female;

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: CA-170<br>Taken orally in a once or twice daily schedule. | Drug: CA-170<br>* Dose escalation stage (Phase 1a) accelerated titration and standard 3+3 dose escalation in patients with advanced solid tumor or lymphoma. Dose expansion stage (Phase 1b) in patients with tumors that are shown to be responsive to anti-PD-1 or anti-PD-L1 checkpoint inhibitors and/or in tumor types known to express PD-L1 or VISTA, including but not limited to: mesothelioma, melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, triple negative breast cancer, head and neck cancer, colorectal cancer, gastric cancer, bladder cancer, and ovarian cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle |  | Approximately 24 months | 
| Maximum tolerated dose (MTD) of CA-170 |  | Approximately 24 months | 
| Recommended Phase 2 Dose (RP2D) of CA-170 |  | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Profile of CA-170 | Maximum Concentration (Cmax) | From Day 1 of Cycle 1(each cycle is 21 days) | 
| Pharmacokinetic (PK) Profile of CA-170 | Area Under the Curve (AUC) | From Day 1 of Cycle 1(each cycle is 21 days) | 
| Preliminary Anti-tumor Activity of CA-170 based on RECIST and Immune Related Response Criterion (irRC) for Solid Tumors or Cheson for Lymphoma |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelioma, PD-L1, VISTA, PD-1