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

NCT02812875 | Completed Phase 1 DMC

• 1 other identifier: CA-170-101
• Study Type: interventional
• Target: 71
• Locations: 4 countries
• Sites: 20

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.

Conditions

Advanced Solid Tumors or Lymphomas

Keywords

Mesothelioma; PD-L1; VISTA; PD-1

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Pharmacokinetic (PK) Profile of CA-170

  From Day 1 of Cycle 1(each cycle is 21 days)

• Pharmacokinetic (PK) Profile of CA-170

  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

Study Arms (1)

CA-170

EXPERIMENTAL

Taken orally in a once or twice daily schedule.

Drug: CA-170

Interventions

CA-170 DRUG

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.

CA-170

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Curis, Inc.: lead

Study Sites (20)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Sarah Cannon Research Institute

Sarasota, Florida, 34232, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Icahn School of Medicine at Mt. Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15237, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Yonsei University Health System - Severance Hospital

Seoul, 3722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Catalan Institute of Oncology

Barcelona, 08907, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Related Publications (2)

• Zong L, Mo S, Sun Z, Lu Z, Yu S, Chen J, Xiang Y. Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer. Mod Pathol. 2022 Feb;35(2):266-273. doi: 10.1038/s41379-021-00901-y. Epub 2021 Sep 7.

  PMID: 34493823 DERIVED

• Li K, Tian H. Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy. J Drug Target. 2019 Mar;27(3):244-256. doi: 10.1080/1061186X.2018.1440400. Epub 2018 Feb 20.

  PMID: 29448849 DERIVED

MeSH Terms

Conditions

Lymphoma; Mesothelioma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: June 24, 2016
• Study Start: May 1, 2016
• Primary Completion: May 7, 2020
• Study Completion: May 7, 2020
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

GB (2); ES (3); KR (4); US (11)