Trial Title:
Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KN510, KN713
NCT ID:
NCT06012708
Condition:
Advanced Solid Tumors
Conditions: Keywords:
Advanced solid tumors
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KN510 60mg/day + KN713 60mg/day
Description:
Once daily with 28 days (4 weeks) as one cycle.
Arm group label:
Dose Level 1
Intervention type:
Drug
Intervention name:
KN510 120mg/day + KN713 60mg/day
Description:
Once daily with 28 days (4 weeks) as one cycle.
Arm group label:
Dose Level 2
Intervention type:
Drug
Intervention name:
KN510 120mg/day + KN713 90mg/day
Description:
Once daily with 28 days (4 weeks) as one cycle.
Arm group label:
Dose Level 3
Intervention type:
Drug
Intervention name:
KN510 120mg/day + KN713 120mg/day
Description:
Once daily with 28 days (4 weeks) as one cycle.
Arm group label:
Dose Level 4
Summary:
To evaluate the safety and tolerability of the combination therapy of KN510 and KN713 and
determine the MTD and RP2D in patients with advanced solid tumors.
Detailed description:
It is expected that KN510 and KN713 will broaden the range of target patient groups and
overcome resistance to the drugs in an innovative manner by targeting the common
metabolic process of cancer cells, unlike existing targeted therapies whose application
is limited depending on the presence of specific mutation and combination of mutations as
they mainly target a single tyrosine kinase.
In this study, the safety and tolerability of combination therapy of KN510 and KN713,
including the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), will be
evaluated in patients with advance solid tumors and based on this, the recommended phase
2 dose (RP2D) will be determined.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male and female adults aged 19-75 years
2. Unresectable advanced or metastatic solid tumors that are confirmed as progressive
disease (PD) after the standard of care currently known to have clinical benefits,
or for which no currently available standard therapies exist due to intolerance,
ineligibility, rejection, etc.
3. At least one measurable lesion per RECIST ver1.1
4. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
5. Life expectancy of at least 12 weeks
6. Confirmed adequate hematologic, renal, and hepatic functions according to the
following criteria (Laboratory tests may be repeated once during the screening
period):
A. Hematological function
- Absolute neutrophil count (ANC) ≥1,500/μL
- Hemoglobin ≥9 g/dL
- Platelet count ≥100,000/μL
B. Renal function: Creatinine clearance (CrCl*) >60 mL/min
*Cockcroft-Gault equation
C. Hepatic function
- Aspartate aminotransferase (AST) ≤3.0 × ULN
- Alanine aminotransferase (ALT) ≤3.0 × ULN (AST/ALT ≤5 × ULN, if hepatic
metastasis is confirmed)
- Total bilirubin ≤1.5 × ULN (with the exception of confirmed Gilbert's syndrome)
D. Coagulation function: Prothrombin time international normalized ratio (PT INR)
and activated partial thromboplastin time (aPTT) ≤1.5 × ULN
7. Voluntary written consent to participate in this study
Exclusion Criteria:
1. Hypersensitivity to the active ingredient or excipients of KN510 or KN713
2. Any of the following medical (surgical) history or comorbidities at the screening
visit:
A. Major surgery that requires general anesthesia or a respiratory assist device
within 4 weeks prior to screening (within 2 weeks for video-assisted thoracoscopic
surgery [VATS] or open-and-closed [ONC] surgery)
B. Clinically significant arrhythmia, acute myocardial infarction, unstable angina,
or NYHA Grade Ⅲ or Ⅳ heart failure within 24 weeks prior to screening
C. Pulmonary thrombosis, deep vein thrombosis, or bronchial asthma, obstructive
pulmonary disease or other life-threatening severe lung disorder (e.g., acute
respiratory distress syndrome, lung failure) considered ineligible for participation
in the study within 24 weeks prior to screening
D. Grade 3 or higher active infectious conditions which require systemic
antibiotics, antivirals, etc. within 2 weeks prior to screening
E. Clinically significantly symptomatic or uncontrolled central nervous system or
brain metastases at screening (except for patients who have discontinued systemic
corticosteroid treatment at least 4 weeks prior to baseline and have been stable for
at least 4 weeks)
F. Hematologic malignancy including lymphoma at screening
G. Uncontrolled hypertension (systolic blood pressure [SBP]/diastolic blood pressure
[DBP] ≥160/100 mmHg) at screening
H. Parkinson's disease, parkinsonian symptoms, tremors, restless leg syndrome, and
other related movement disorders at screening
I. Active hepatitis B* or C† at screening
* Defined as HBsAg positive at screening; patients on stable antiviral regimen may
participate
† Defined as HCV Ab positive at screening; patients who test negative for HCV RNA
may participate
J. Known human immunodeficiency virus (HIV) infection
K. Difficulty (e.g., problem swallowing) in oral administration of KN510 and KN713
or disease (celiac disease, Crohn's disease, or intestinal resection which is
clinically significant or impacts absorption) which impacts absorption at screening
L. History or suspected symptoms of gastroesophageal reflux disease (GERD) such as
gastric ulcer, duodenal ulcer, and reflux esophagitis at screening
M. History of autoimmune diseases at screening
N. Deemed ineligible for the study for having a comorbidity that is uncontrolled or
requires treatment
3. Prior treatment with any of the following medications within 2 weeks prior to
screening
A. Proton pump inhibitors (PPIs) other than the IP
B. Strong CYP2C19 inducers: Rifampicin, Apalutamide, Rifamycin, Rifaximin,
Rifapentine
C. Strong CYP2C19 inhibitors: Fluvoxamine, Ticlopidine, Chloramphenicol,
Delavirdine, Gemfibrozil, Stiripentol, Fluoxetine, Imipramine, Clomipramine,
Lansoprazole, Isoniazid, Zafirlukast, Tioconazole, Miconazole
D. CYP2C19 substrates: Clopidogrel, Citalopram, Cilostazol, Phenytoin, Diazepam
E. Vitamin K antagonists: Warfarin, Dicoumarol, Phenindione, Phenprocoumon,
Acenocoumarol, Ethyl biscoumacetate, Fluindione, Clorindione, Diphenadione,
Tioclomarol
F. Antiretrovirals: Rilpivirine-containing products, Atazanavir, Nelfinavir,
Saquinavir
G. High dose Methotrexate (≥1000 mg/m2)
H. Digoxin
I. Cefditoren, Cefuroxime
J. Levoketoconazole
K. St John's Wort
L. Bromopride, Metoclopramide
M. Other anti-cancer therapies (chemotherapy, radiotherapy, immunotherapy, targeted
therapy, hormone therapy, etc. other than the IP) which could impact the efficacy
results during the study (However, local radiotherapy to alleviate ostalgia,
bronchial obstruction, skin lesion, etc. are permitted. The total irradiation dose
must be within the site-specific reference range for palliative therapy, and
irradiation sites must be excluded from the tumor assessment.)
N. Requiring continued treatment with systemic corticosteroids at a dose of
prednisone >10 mg/day or equivalent (with exceptions of topical use such as
intra-articular, intranasal, intraocular, and inhalational administration and
temporary use for treatment and prevention of allergic reactions to a contrast agent
or AEs [e.g., vomiting])
4. Pregnant or lactating women, or women of childbearing potential and men who are
unwilling to remain abstinent or use adequate methods of contraception* during the
study and for 3 months after IP administration
* Adequate methods of contraception:
- Hormonal contraceptives
- Placement of an intrauterine device or intrauterine system
- Surgical sterilization (vasectomy, tubal ligation, etc.)
5. Received/Used another investigational agent/device within 4 weeks (or 5 half-lives)
prior to screening
6. Ineligibility or inability to participate in the study in the judgment of the
investigator
Gender:
All
Minimum age:
19 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Center
Address:
City:
Goyang-si
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Sang Myung Woo, PI
Phone:
031-920-0743
Email:
73324@ncc.re.kr
Start date:
September 11, 2023
Completion date:
December 2024
Lead sponsor:
Agency:
New Cancer Cure-Bio Co.,Ltd.
Agency class:
Industry
Source:
New Cancer Cure-Bio Co.,Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06012708
