To evaluate the safety, tolerability, pharmacokinetics and antitumor activity of YYB101 with Irinotecan, patients who are metastatic or recurrent Colorectal Cancer Patients.
Metastatic or recurrent colorectal cancer patients will be enrolled to evaluate the safety, tolerability, pharmacokinetics, and efficacy of YYB101 in combination with irinotecan. In Phase 1b, YYB101 20 mg/kg in combination with irinotecan 150 mg/m2 will be administered as a dose level 0, and the safety and pharmacokinetic assessments will be performed based on the DLT after a 4-week treatment period. If no DLT occurs during the 4-week observation period, dosing will be continued every 2 weeks until progressive disease (PD) or unacceptable toxicity occurs. After completion of Phase 1b, the SRC will determine the RP2D of YYB101 and irinotecan, and Phase 2a will be initiated. Stage 2 will proceed when unconfirmed response is observed in one or more subjects out of 10 subjects evaluable for tumor in Phase 2a Stage 1 which includes the RP2D dose cohort in Phase 1b.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
1. b (Dose level 0 cohort): YYB101 20mg/kg, Irinotecan 150 mg/m2 of each dose level, IV infusion on Day 1, Day15, and followed by every 2 weeks until disease progression or unacceptable toxicity 2. a Stage 1: YYB101 RP2D, Irinotecan 150 mg/m2 of each dose level, IV infusion on Day 1, Day15, and followed by every 2 weeks until disease progression or unacceptable toxicity
Samsung Medical Center
Seoul, Gangnam-gu, South Korea
National Cancer Center
Seoul, Goyang-si, Gyeonggi-do, South Korea
Seoul ST. Mary's Hospital
Seoul, Seocho-gu, South Korea
1b (Dose level 0) cohort: Safety, Tolerability of YYB101 by DLTs and MTD
DLTs and MTD
Time frame: 28 days
2a cohort: Safety, Tolerability of YYB101 by ORR
ORR
Time frame: By 12 months after enrollment of the last subject
1b (Dose level 0) cohort
Safety and tolerability (MTD/RP2D based by DLT, Incidence of AEs that result in discontinuation and dose reduction of YYB101, Clinical laboratory abnormalities that result in discontinuation and dose reduction of YYB101, Vital sign that result in discontinuation and dose reduction of YYB101, Anti-YYB101 antibody that result in discontinuation and dose reduction of YYB101)
Time frame: By 12 months after enrollment of the last subject
1b (Dose level 0) cohort
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
Time frame: By 12 months after enrollment of the last subject
1b (Dose level 0) cohort
Pharmacokinetics: Peak Plasma Concentration (Cmax)
Time frame: By 12 months after enrollment of the last subject
1b (Dose level 0) cohort
Pharmacokinetics: Serum HGF Concentration profile
Time frame: By 12 months after enrollment of the last subject
1b (Dose level 0) cohort
Antitumor activity of YYB101 and Irinotecan (Tumor response result evaluted by RECIST version 1.1)
Time frame: By 12 months after enrollment of the last subject
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2a cohort
Progression-free survival (PFS) will be measured using RECIST version 1.1
Time frame: By 12 months after enrollment of the last subject
2a cohort
Disease Control Rate (DCR) will be measured using RECIST version 1.1
Time frame: By 12 months after enrollment of the last subject
2a cohort
Duration Of Response (DOR) will be measured using RECIST version 1.1
Time frame: By 12 months after enrollment of the last subject
2a cohort
Overall Survival (OS) will be measured using RECIST version 1.1
Time frame: By 12 months after enrollment of the last subject
2a cohort
Safety profile (Incidence of AEs that result in discontinuation and dose reduction of YYB101, Clinical laboratory abnormalities that result in discontinuation and dose reduction of YYB101, Vital sign that result in discontinuation and dose reduction of YYB101, Anti-YYB101 antibody that result in discontinuation and dose reduction of YYB101)
Time frame: By 12 months after enrollment of the last subject
2a cohort
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
Time frame: By 12 months after enrollment of the last subject
2a cohort
Pharmacokinetics: Peak Plasma Concentration (Cmax)
Time frame: By 12 months after enrollment of the last subject
2a cohort
Pharmacokinetics: Serum HGF Concentration profile \[only stage 1 subject\]
Time frame: By 12 months after enrollment of the last subject