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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors or Lymphomas
• Intervention / Treatment: Drug: CA-170

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 3722
    • Yonsei University Health System - Severance Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Barcelona, Spain, 08907
    • Catalan Institute of Oncology
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' NHS Foundation Trust
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Sarasota, Florida, United States, 34232
      • Sarah Cannon Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15237
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CA-170; Taken orally in a once or twice daily schedule.

Drug: CA-170; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Curis, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): May 7, 2020
• Study Completion (Actual): May 7, 2020

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 22, 2016
• First Posted (Estimate): June 24, 2016

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; Mesothelioma; VISTA
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: CA-170-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided