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

Advanced Solid Tumors or Lymphomas Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02812875
• Other study ID #: CA-170-101
• Status: Completed
• Phase: Phase 1
• Start date: May 2016
• Est. completion date: May 7, 2020

Study information

• Verified date: June 2020
• Source: Curis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: May 7, 2020
• Est. primary completion date: May 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Advanced Solid Tumors or Lymphomas
• Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Spain	Catalan Institute of Oncology	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United States	Northwestern University	Chicago	Illinois
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Sarah Cannon Research Institute	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Curis, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle		Approximately 24 months
Primary	Maximum tolerated dose (MTD) of CA-170		Approximately 24 months
Primary	Recommended Phase 2 Dose (RP2D) of CA-170		Approximately 24 months
Secondary	Pharmacokinetic (PK) Profile of CA-170	Maximum Concentration (Cmax)	From Day 1 of Cycle 1(each cycle is 21 days)
Secondary	Pharmacokinetic (PK) Profile of CA-170	Area Under the Curve (AUC)	From Day 1 of Cycle 1(each cycle is 21 days)
Secondary	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