Clinical trial NCT02812875: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors or Lymphomas
Keywords: Mesothelioma
PD-L1
VISTA
PD-1
Lead sponsor: Curis, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-24
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle
timeFrame: Approximately 24 months
measure: Maximum tolerated dose (MTD) of CA-170
timeFrame: Approximately 24 months
measure: Recommended Phase 2 Dose (RP2D) of CA-170
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Pharmacokinetic (PK) Profile of CA-170
timeFrame: From Day 1 of Cycle 1(each cycle is 21 days)
measure: Pharmacokinetic (PK) Profile of CA-170
timeFrame: From Day 1 of Cycle 1(each cycle is 21 days)
measure: Preliminary Anti-tumor Activity of CA-170 based on RECIST and Immune Related Response Criterion (irRC) for Solid Tumors or Cheson for Lymphoma
timeFrame: 36 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
References:
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.
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.