Phase 1,Two-part (Dose Escalation, Dose Expansion), Multicenter,Non-randomized,Open-label, Multiple Dose, First-in-human Study of CA102N Monotherapy and of CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 37
- Locations
- 3
- Primary Endpoint
- Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Study Overview
Brief Summary
Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors.
CA102N will be evaluated in subjects with locally advanced or metastatic solid tumours for which no effective therapy is available in Part 1 (dose escalation) and in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer (mCRC) after prior oxaliplatin and irinotecan-based chemotherapy in Part 2 (dose expansion).
Detailed Description
Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors.
Part 1 (dose escalation) will determine the safety and tolerability of three dose levels of CA102N as monotherapy and the safety, tolerability and preliminary recommended phase 2 dose (RP2D) of CA102N in combination with trifluridine/tipiracil (LONSURF) in patients with locally advanced or metastatic solid tumors.
Part 2 (dose expansion) will further investigate the safety and tolerability of the combination of CA102N and trifluridine/tipiracil (LONSURF) at the preliminary RP2D in patients with locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and if RAS wild-type metastatic colorectal cancer, an anti-epidermal growth factor receptor (EGFR) therapy..
Preliminary efficacy will be evaluated in Parts 1 and 2 of the study as an exploratory endpoint.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects enrolled in Part 1 must have histologically documented locally advanced or metastatic solid tumor for which there is no effective therapy available.
- •Subjects enrolled in Part 2 must have histologically documented locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
- •Age ≥18 years (US) or ≥20 years (Taiwan).
- •ECOG performance status 0-
- •Measurable or non-measurable disease based on RECIST version 1.
- •Subjects enrolled in Part 2 must have at least one measurable lesion.
- •Adequate organ function within 14 days before 1st dose of study drug, defined as:
- •Platelet count ≥ 100,000/mm
- •Hemoglobin ≥ 9.0 g/dL.
- •Absolute neutrophil count ≥ 1500/mm3 (without hematopoietic growth factor support).
- •Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation.
- •Aspartate aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
- •Alanine aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
- •Total bilirubin ≤1.5 x ULN (unless documented Gilbert's Syndrome).
- •Has had an adequate treatment washout period prior to 1st dose of study drug defined as:
- •No major surgery within the past 4 weeks.
- •No extended field radiation therapy within the prior 4 weeks.
- •No anticancer therapy or bevacizumab within the prior 3 weeks.
- •No investigational agent received within prior 4 weeks (or 5 times the half-life of the investigational agent, whichever is shorter).
- •No aspirin or NSAIDs for at least 72 hours before 1st dose of study drug.
- •No herbal supplements taken as anticancer agents within the prior 7 days.
- •Able to provide written informed consent.
- •Life expectancy of ≥ 3 months.
- •Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective means of contraception from study entry through at least 6 months after the last dose of CA102N. Women of childbearing potential are those women who have not been permanently sterilized or are not postmenopausal.
Exclusion Criteria
- •For Part 2, active malignancies other than colorectal cancer.
- •History of hypersensitivity or hepatotoxic reaction to nimesulide or to any excipient.
- •Requiring therapeutic doses of anticoagulants.
- •History or presence of a bleeding tendency or disorder.
- •History of gastrointestinal bleed or perforation related to previous NSAID therapy.
- •Presence or history of recurrent peptic ulcer or hemorrhage.
- •History of cerebrovascular or other active bleeding.
- •Myocardial infarction within the last 12 months, severe or unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) Class III or IV.
- •History of a serious cardiac arrhythmia requiring treatment.
- •Corrected QT prolongation using Fridericia formula (QTcF), of > 450 msec for males or > 470 msec for females based on a triplicate 12-lead ECG.
- •Clinically significant lung disease (eg, interstitial pneumonia, interstitial lung disease, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) requiring continuous systemic corticosteroid treatment for 6 months before registration or who are suspected to have such diseases by imaging at Screening.
- •Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks.
- •Active autoimmune disease that has required systemic treatment in past 2 years.
- •History of allogeneic transplantation requiring immunosuppressive therapy.
- •Known positive test for hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV).
- •Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
- •Pregnant or breast feeding.
- •Unresolved toxicity of greater than or equal to NCI-CTCAE (version 5.0) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).
- •Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator.
Arms & Interventions
Dose Escalation - CA102N Monotherapy
0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 of a 28-day cycle
Intervention: CA102N (Drug)
Dose Escalation - CA102N plus LONSURF
0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle
Intervention: CA102N (Drug)
Dose Escalation - CA102N plus LONSURF
0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle
Intervention: LONSURF (Drug)
Dose Expansion - CA102N plus LONSURF
The preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle
Intervention: CA102N (Drug)
Dose Expansion - CA102N plus LONSURF
The preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle
Intervention: LONSURF (Drug)
Outcomes
Primary Outcomes
Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Time Frame: The safety measures will be assessed and recorded throughout the trial until 30 days following treatment termination (an average of 1 year).
The primary endpoint for the study is the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF) as determined according to the NCI-CTCAE version 5.0.
Secondary Outcomes
- Serum concentration of CA102N(Serum sampling timepoints: predose, 0.5,1, 2, 4, 8, 12, 24, 48, and 72 hours postdose CA102N on Days 1 and 15 at Cycle 1 (each cycle is 28 days).)