This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer after first-line treatment. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Phase Ib will use a standard 3+3 scheme with the planned doses of T-DXd (4.4\~6.4 mg/kg) once every 3 weeks in combination with Ramucirumab 8mg/kg administered once every 2 weeks. * Dosing Regimen * Trastruzumab deruxtecan : One IV infusion every 3 weeks on Day 1 of each 21-day cycle * Ramucirumab : One IV infusion on every 2 weeks on Day 1,15 of each 28-day cycle
Sun Young Rha
Seoul, Seoul, South Korea
RECRUITINGRP2D
Maximum Tolerated dose (MTD) and Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).
Time frame: within first 6 weeks of treatment
PFS rate at 24 weeks
Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria. Determination of PFS rate at 24 weeks.
Time frame: within first 2 4weeks of treatment
Overall Survival (OS)
Defined from the date of treatment assignment until the date of death due to any cause. Any participant not known to have died at the time of analysis will be censored based on the last recorded date on which the participant was known to be alive.
Time frame: 6 months after the last treatment of the last subject
Objective Response Rate (ORR)
Defined as the proportion of participants with measurable disease who achieve complete response(CR) or partial response(PR), as determined by the Investigator per RECIST v1.1. Data obtained up until disease progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR. Confirmatory scan is needed for the patients with CR or PR after 4 weeks of the first response. Participants who discontinue treatment without progression, receive a subsequent therapy, and then respond, will not be included as responders in the ORR.
Time frame: 6 months after the last treatment of the last subject
Disease Control Rate (DCR)
Defined as the percentage of participants who have a confirmed CR or PR or who have SD (without subsequent cancer therapy) after the date of treatment assignment.
Time frame: 6 months after the last treatment of the last subject
Duration of Response (DoR)
Defined as the percentage of participants who have a confirmed CR or PR or who have SD (without subsequent cancer therapy) after the date of treatment assignment.
Time frame: 6 months after the last treatment of the last subject
Progression-free survival (PFS)
Defined as time from the date of treatment assignment until progression per RECIST v1.1 as assessed by the Investigator, or death due to any cause. Participants who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment.
Time frame: 6 months after the last treatment of the last subject
adverse events categorized in accordance with CTCAE 5.0 Criteria.
Safety and tolerability
Time frame: 6 months after the last treatment of the last subject
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