Advanced Solid Tumors or Lymphomas
Conditions
Keywords
Mesothelioma, PD-L1, VISTA, PD-1
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.
Interventions
DRUGCA-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.
Sponsors
Curis, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Profile of CA-170 | From Day 1 of Cycle 1(each cycle is 21 days) | Maximum Concentration (Cmax) |
| 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 | — |
Countries
South Korea, Spain, United Kingdom, United States
Outcome results
None listed