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

Phase 1

Completed

• Conditions: Advanced Solid Tumors or Lymphomas
• Interventions: Drug: CA-170

• Registration Number: NCT02812875
• Lead Sponsor: Curis, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-06-14
• Study First Submitted QC: 2016-06-22
• Study First Posted: 2016-06-24
• Primary Completion: 2020-05-07
• Study Completion: 2020-05-07
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-24
• Last Update Posted: 2020-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

Inclusion Criteria

1. Males and females ≥ 18 years of age;
2. Life expectancy of at least 3 months;
3. ECOG PS ≤ 1;
4. Acceptable bone marrow and organ function at screening;
5. Ability to swallow and retain oral medications;
6. Negative serum pregnancy test in women of childbearing potential;
7. Measurable disease;
8. 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

1. Prior treatment anti-cancer therapy or use of any investigational agent within the past 28 days or 5 half-lives, whichever is shorter;
2. Toxicity from prior chemotherapy that has not resolved to Grade ≤ 1;
3. Radiotherapy within the last 21 days;
4. Primary brain tumors or CNS metastases;
5. Major or minor surgery < 28 and <14 days from the start of treatment, respectively;
6. Active autoimmune disease or any medical condition requiring the use of systemic immunosuppressive medications;
7. Endocrinopathies, unless on stable hormone replacement therapy;
8. Active infection requiring systemic therapy;
9. Receipt of live vaccines against infectious diseases within 28 days;
10. HIV positive or an AIDS-related illness;
11. Active/chronic HBV or HCV infection;
12. Uncontrolled CHF (NYHA Class 2-4), angina, MI, CVA, coronary/peripheral artery bypass graft surgery, TIA, or PE in prior 3 months;
13. Cardiac dysrhythmias;
14. Gastrointestinal disease that interferes with receipt of oral drugs;
15. Concomitant malignancy;
16. Pregnant or lactating female;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CA-170	CA-170	Taken orally in a once or twice daily schedule.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Profile of CA-170	From Day 1 of Cycle 1(each cycle is 21 days)	Area Under the Curve (AUC)
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

Trial Locations

Locations (19)

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom

Yonsei University Health System - Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Catalan Institute of Oncology; 🇪🇸 Barcelona, Spain

Icahn School of Medicine at Mt. Sinai; 🇺🇸 New York, New York, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Clinic i Provincial; 🇪🇸 Barcelona, Spain

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom