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

Primary Purpose

Advanced Solid Tumors or Lymphomas

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CA-170
Sponsored by
Curis, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors or Lymphomas focused on measuring Mesothelioma, PD-L1, VISTA, PD-1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • University of California San Francisco
  • Sarah Cannon Research Institute at HealthONE
  • Sarah Cannon Research Institute
  • Northwestern University
  • Karmanos Cancer Institute
  • Icahn School of Medicine at Mt. Sinai
  • Memorial Sloan Kettering Cancer Center
  • Carolina BioOncology Institute
  • University of Pittsburgh Medical Center
  • Sarah Cannon Research Institute
  • University of Texas MD Anderson Cancer Center
  • Seoul National University Hospital
  • Samsung Medical Center
  • Yonsei University Health System - Severance Hospital
  • Asan Medical Center
  • Hospital Clinic i Provincial
  • Catalan Institute of Oncology
  • Hospital Universitario 12 de Octubre
  • Cambridge University Hospitals NHS Foundation Trust
  • Guy's and St Thomas' NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CA-170

Arm Description

Taken orally in a once or twice daily schedule.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Pharmacokinetic (PK) Profile of CA-170
Maximum Concentration (Cmax)
Pharmacokinetic (PK) Profile of CA-170
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

Full Information

First Posted
June 14, 2016
Last Updated
June 24, 2020
Sponsor
Curis, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02812875
Brief Title
A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 7, 2020 (Actual)
Study Completion Date
May 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Curis, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors or Lymphomas
Keywords
Mesothelioma, PD-L1, VISTA, PD-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CA-170
Arm Type
Experimental
Arm Description
Taken orally in a once or twice daily schedule.
Intervention Type
Drug
Intervention Name(s)
CA-170
Intervention Description
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.
Primary Outcome Measure Information:
Title
The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle
Time Frame
Approximately 24 months
Title
Maximum tolerated dose (MTD) of CA-170
Time Frame
Approximately 24 months
Title
Recommended Phase 2 Dose (RP2D) of CA-170
Time Frame
Approximately 24 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Profile of CA-170
Description
Maximum Concentration (Cmax)
Time Frame
From Day 1 of Cycle 1(each cycle is 21 days)
Title
Pharmacokinetic (PK) Profile of CA-170
Description
Area Under the Curve (AUC)
Time Frame
From Day 1 of Cycle 1(each cycle is 21 days)
Title
Preliminary Anti-tumor Activity of CA-170 based on RECIST and Immune Related Response Criterion (irRC) for Solid Tumors or Cheson for Lymphoma
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Sarah Cannon Research Institute at HealthONE
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Icahn School of Medicine at Mt. Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Carolina BioOncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15237
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Yonsei University Health System - Severance Hospital
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
5505
Country
Korea, Republic of
Facility Name
Hospital Clinic i Provincial
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Catalan Institute of Oncology
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34493823
Citation
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.
Results Reference
derived
PubMed Identifier
29448849
Citation
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.
Results Reference
derived

Learn more about this trial

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

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