The KN510713 Study in Combination With mFOLFIRINOX

Официальное название

An Open-label, Dose-finding and Dose-expansion, Phase I/IIa Clinical Trial to Evaluate the Safety and Efficacy of KN510713 in Combination With mFOLFIRINOX in Patients With Locally Advanced or Metastatic Pancreatic Cancer

Обзор

This study is designed to evaluate the safety and efficacy of KN510713 in combination with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. The study will be conducted in two parts: Part 1 (Dose-finding) and Part 2 (Dose expansion).

Вмешательства

• Препарат Study drug: KN510 120mg/day + KN713 90mg/day, Combination Chemotherapy: mFOLFIRINOX
  KN510 120mg/day + KN713 90mg/day: once daily in 14-day (2-week) cycles. mFOLFIRINOX: Treatment is repeated every 2 weeks
• Препарат Study drug: KN510 120mg/day + KN713 120mg/day, Combination Chemotherapy: mFOLFIRINOX
  KN510 120mg/day + KN713 120mg/day: once daily in 14-day (2-week) cycles. mFOLFIRINOX: Treatment is repeated every 2 weeks

Первичные конечные точки

• Number of occurrences, affected subjects with adverse events. [Срок оценки: Through study completion, an average of 12 months]
• The frequency and percentage of Dose-Limiting Toxicitys [Срок оценки: 4 weeks]

Вторичные конечные точки (5)

• Objective Response Rate [Срок оценки: Through study completion, an average of 12 months]
• Disease Control Rate [Срок оценки: Through study completion, an average of 12 months]
• Duration of Response [Срок оценки: Through study completion, an average of 12 months]
• Progression-Free Survival [Срок оценки: Through study completion, an average of 12 months]
• Overall Survival [Срок оценки: Through study completion, an average of 12 months]

Критерии участия

Критерии включения

• Adult male and female subjects aged 19 to 75 years at the time of providing written informed consent
• Subjects with histologically or cytologically confirmed unresectable, locally advanced or metastatic PDAC who are scheduled to receive treatement with mFOLFIRINOX
• Subjects who have not received prior systemic chemotherapy for locally advanced or metastatic pancreatic cancer (Note: Prior neo-adjuvant or adjuvant systemic chemotherapy is allowed if there was no disease progression within 6 months after the last dose of chemotherapy)
• Subjects with at least one measurable lesion according to RECIST ver1.1
• Subjects with an ECOG performance status of 0 or 1
• Subjects with an expected survival of at least 12 weeks
• Subjects with adequate hematologic function, renal and hepatic function, and coagulation function based on the following laboratory criteria (only one repeat of laboratory tests is permitted during the screening period)
• Subjects who have been informed about the clinical study and voluntarily signed the written informed consent form

Критерии исключения

1\) Known hypersensitivity to the IP, combination anticancer agents, their components, or drugs of a similar class 2) Subjects with any of the following medical history, or surgical/procedural history identified:

• History of any malignancy other than pancreatic cancer within 5 years prior to screening (Subjects with a history of basal cell carcinoma, squamous cell carcinoma of the skin, thyroid cancer, or carcinoma in situ at other sites may be eligible if the cancer was successfully treated and there has been no recurrence for more than 3 years, as determined by the investigator).
• Major surgery requiring general anesthesia or ventilatory support within 4 weeks prior to baseline (Video-assisted thoracoscopic surgery (VATS) or ONC surgery is limited to 2 weeks).
• Clinically significant arrhythmia, acute myocardial infarction, unstable angina, or NYHA class III or IV heart failure within 24 weeks prior to baseline.
• Pulmonary thrombosis, deep vein thrombosis, or other serious, life-threatening pulmonary diseases (e.g., acute respiratory distress syndrome, lung failure), or conditions such as asthma or COPD considered inappropriate for study participation, occurring within 24 weeks prior to baseline.
• Known DPD deficiency
• Subjects known to carry the genetic polymorphism of UGT1A1\*6 or UGT1A1\*28 as homozygotes (UGT1A1\*6/\*6 or UGT1A1\*28/\*28) or as compound heterozygotes (UGT1A1\*6/\*28)
• Known fructose intolerance 3) Comorbidities or conditions as follows:

(1) Peripheral neuropathy of moderate (Grade 2) or higher (2) Chronic diarrhea or inflammatory bowel disease (Crohn's disease, ulcerative colitis) (3) Ileus or Intestinal obstruction (4) Clinically significant symptoms of ILD or pulmonary fibrosis requiring steroid therapy (5) Chronic kidney disease requiring dialysis (6) Clinically significant symptomatic or uncontrolled central nervous system or brain metastases (permitted if systemic corticosteroids were discontinued ≥4 weeks prior to baseline and the metastases have remained stable for ≥4 weeks) (7) Uncontrolled hypertension (SBP/DBP ≥160/100 mmHg) (8) QTc >450 ms on ECG (9) Active hepatitis B or hepatitis C (10) Known HIV infection (11) Conditions interfering with oral intake (e.g., dysphagia) or absorption (e.g., celiac disease, Crohn's disease, or a clinically significant bowel resection that may affect drug absorption) (12) Subjects with a history or suspected symptoms of gastro-esophageal reflux disease (GERD), including gastric ulcer, duodenal ulcer, or reflux esophagitis (13) Parkinson's disease, parkinsonism, tremor, restless leg syndrome, or other related movement disorders (14) Clinically significant symptomatic or uncontrolled ascites or pleural effusion (15) Subjects who, in the investigator's judgment, have a disease or condition sufficiently serious to influence the study results, or for whom the concomitant anticancer agents are contraindicated 4) Prior medications or treatments as follows:

• Radiotherapy within 2 weeks prior to screening (radiotherapy for symptom relief or bone lesions at high risk of pathological fracture is allowed if completed ≥1 week before the planned enrollment, provided that the treated lesions is not selected as target lesions for RECIST evaluation)
• Use of PPIs other than the IP within 2 weeks prior to screening
• Administration of any antithrombotic agents, including antiplatelet or anticoagulant drugs, within 2 weeks prior to screening, or an anticipated need for such medication during the study period (the use of low-molecular-weight heparin \[LMWH\] for prophylaxis or management of venous thrombosis is permitted during the study)
• Use of rilpivirine-containing products within 2 weeks prior to screening
• Use of atazanavir-containing products within 2 weeks prior to screening
• Current administration of, or anticipated need for strong CYP3A4 inhibitors or inducers
• Current administration of, or anticipated need for CYP2C19 substrates, strong inhibitors, or inducers
• High dose methotrexate (≥1000 mg/m2)
• St. John's wort
• Requirement for continuous use (≥4 weeks) of systemic corticosteroids equivalent to >10 mg/day prednisone (local administration such as intra-articular, intranasal, ophthalmic, or inhaled corticosteroids, and short-term use for the treatment or prophylaxis of contrast-media allergy or AEs \[e.g., vomiting\] are permitted)
• Current administration of, or anticipated need for sorivudine 5) Pregnant or breastfeeding women, or women of childbearing potential and men who are unwilling to remain abstinent or use appropriate contraception until 12 months (for men) or 15 months (for women) after the last administration of IP/concomitant medication following study enrollment 6) Participation in another clinical trial and administration or application of an investigational drug or device within 4 weeks prior to screening 7) Any other subject who, in the investigator's judgment, is unsuitable for participation in this study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• National Cancer Center — Goyang-si

Идентификаторы

NCT: NCT07114861 · NCCKN-101-P2a

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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