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

• ClinicalTrials.gov Identifier: NCT02812875
• Recruitment Status: Completed
• First Posted: June 24, 2016
• Last Update Posted: June 26, 2020
• Sponsor: Curis, Inc.
• Information provided by (Responsible Party): Curis, Inc.

Tracking Information

• First Submitted Date: June 14, 2016
• First Posted Date: June 24, 2016
• Last Update Posted Date: June 26, 2020
• Study Start Date: May 2016
• Actual Primary Completion Date: May 7, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2018)

• The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle [ Time Frame: Approximately 24 months ]
• Maximum tolerated dose (MTD) of CA-170 [ Time Frame: Approximately 24 months ]
• Recommended Phase 2 Dose (RP2D) of CA-170 [ Time Frame: Approximately 24 months ]

Original Primary Outcome Measures (submitted: June 22, 2016)

• The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle [ Time Frame: 43 weeks ]
• Maximum tolerated dose (MTD) of CA-170 [ Time Frame: 21 Days ]
• Recommended Phase 2 Dose (RP2D) of CA-170 [ Time Frame: Approximately 18 months ]

Current Secondary Outcome Measures (submitted: October 26, 2018)

• Pharmacokinetic (PK) Profile of CA-170 [ Time Frame: From Day 1 of Cycle 1(each cycle is 21 days) ]
  Maximum Concentration (Cmax)
• Pharmacokinetic (PK) Profile of CA-170 [ Time Frame: From Day 1 of Cycle 1(each cycle is 21 days) ]
  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 [ Time Frame: 36 months ]

Original Secondary Outcome Measures (submitted: June 22, 2016)

• Maximum Concentration (Cmax) [ Time Frame: From Day 1 of Cycle 1(each cycle is 21 days) ]
• Area Under the Curve (AUC) [ Time Frame: From Day 1 of Cycle 1(each cycle is 21 days) ]
• Exploratory Outcome Measure: Preliminary clinical efficacy based on RECIST [ Time Frame: 1 year ]
• Exploratory Outcome Measure: Preliminary clinical efficacy based on irRECIST [ Time Frame: 1 year ]
• Exploratory Outcome Measure: Preliminary clinical efficacy based on Cheson [ Time Frame: 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors or Lymphomas

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.

Study Arms

Experimental: CA-170

Taken orally in a once or twice daily schedule.

Intervention: Drug: CA-170

• Publications *: 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. Review.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 24, 2020): 71
• Original Estimated Enrollment (submitted: June 22, 2016): 150
• Actual Study Completion Date: May 7, 2020
• Actual Primary Completion Date: May 7, 2020 (Final data collection date for primary outcome measure)

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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02812875
• Other Study ID Numbers: CA-170-101
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Curis, Inc.
• Study Sponsor: Curis, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Curis, Inc.
• Verification Date: June 2020