T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age19+
SponsorYonsei University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Able and willing to give written informed consent and has signed the appropriate weitten informed consent form(ICF) prior to performance of any trial activityes.
Eligible male and female subjects aged ≥19 years.
Histologically or cytologically proven metastatic or locally advanced HER2 low gastric or GEJ adenocarcinoma: The definition of HER2 low is 1+ by immunohistochemistry (IHC) or 2+ by IHC and without HER2 gene amplification (negative by in situ hybridization[ISH]).
Progressed after 1st line palliative treatment. Adjuvant chemotherapy will be counted as 1st line treatment if the cancer has recurred within 6 months of completion of adjuvant chemotherapy.
Disqualifiers
Anticancer treatment within 14 days before the start of trial treatment.
Major surgery within 28 days before the start of trial treatment.
Have received more than 2 prior lines of chemotherapy.
Grade ≥ 2 peripheral neuropathy.
Trial design
Design model
Single group
Treatments tested in this trial
T-Dxd(Trastuzmab deruxtecan), Ramucirumab
DrugPhase 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
Treatment groups
58 Participants
are divided into 1 treatment groupGroup A: Single arm, Trastruzumab deruxtecan, RamucirumabOther 1 intervention
Trial outcomes
Primary outcomes
1
RP2D
Maximum Tolerated dose (MTD) and Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).
Time frame
within first 6 weeks of treatment2
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 treatmentSecondary outcomes
1
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 subject2
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 subject3
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 subject4
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 subjectSponsors and contacts
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Source ClinicalTrials.gov