Ovarian, fallopian tube, and peritoneal cancers are often diagnosed at an advanced stage, requiring chemotherapy. Recently, the standard treatment, platinum-based chemotherapy plus PARP inhibitors, has extended disease-free survival (PFS). However, most patients eventually develop resistance to PARP inhibitors and become unresponsive to conventional treatments. Therefore, an effective standard treatment for patients who relapse after PARP inhibitor resistance has not yet been established. Meanwhile, HER2 protein expression has been identified in some patients, drawing attention as a new therapeutic target. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2, has already demonstrated efficacy and safety in other HER2-positive cancers. This study aimed to explore the potential of T-DXd as a new treatment option by evaluating the efficacy and safety of T-DXd in patients with ovarian, fallopian tube, and peritoneal cancer who relapsed after PARP inhibitor treatment and who express HER2. Participants will: * Arm A: T-DXd +/- Bevacizumab, IV, every 3weeks * Arm B: Platinum-based chemotherapy +/- Bevacizumab, IV
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
116
Trastzumab deruxtecan will be administrated via intravenous, every 3 weeks.
Bevacizumab is administered intravenously in one of two doses: 1. 10 mg/kg every 2 weeks 2. 15 mg/kg every 3 weeks 1. 10mg/kg, every 2weeks 2. 15mg/kg, every 3weeks
\*Proposed regimens for Arm B 1. PLD 30\~40mg/m2 D1 + Carboplatin AUC 5 D1 +/- bevacizumab 10mg/kg D1/D15 q4w (for 6-8 cycles) followed by bevacizumab 15mg/kg q3w 2. Paclitaxel 175mg/m2 D1 + Carboplatin AUC 5 D1 +/- bevacizumab 15mg/kg D1 q3w (for 6-8 cycles) followed by bevacizumab 15mg/kg q3w 3. Gemcitabine 1000mg/m2 D1/D8 + Carboplatin AUC 4 or 5 D1 +/- bevacizumab 15mg/kg D1 q3w (for 6-8 cycles) followed by bevacizumab 15mg/kg q3w
Yonsei University Health System, Severance Hospital
Seoul, Seoul, South Korea
Progression Free Survival (PFS) in HER2 IHC 1+/2+/3+ population
Defined as the time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Progression Free Survival (PFS) in HER2 IHC 2+/3+ population
Defined as the time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Objective Response Rate (ORR) by investigator in HER2 2+/3+ population
Defined as the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Objective Response Rate (ORR) by investigator in HER2 1+/2+/3+ population
Defined as the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Disease control rate (DCR) by investigator in HER2 2+/3+ population
Defined as the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . SD must be achieved at ≥ 7 weeks after randomization to be considered best overall response.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Disease control rate (DCR) by investigator in HER2 1+/2+/3+ population
Defined as the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . SD must be achieved at ≥ 7 weeks after randomization to be considered best overall response.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Clinical benefit rate (CBR) by investigator in HER2 2+/3+ population
Defined as the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . (duration of SD ≥ 23 weeks after randomization)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Clinical benefit rate (CBR) by investigator in HER2 1+/2+/3+ population
Defined as the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . (duration of SD ≥ 23 weeks after randomization)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Duration of Response Rate (DoR) by investigator in HER2 2+/3+ population
Measured from the time of initial response until documented tumor progression.
Time frame: From the time of first documentation of CR or PR until the time of first documentation of subsequent PD or death from any cause, whichever came first, assessed up to 5 years.
Duration of Response Rate (DoR) by investigator in HER2 1+/2+/3+ population
Measured from the time of initial response until documented tumor progression.
Time frame: From the time of first documentation of CR or PR until the time of first documentation of subsequent PD or death from any cause, whichever came first, assessed up to 5 years.
Time to first subsequent treatment (TFST) Time to second Subsequent Treatment (TSST) in HER2 2+/3+ population
Defined as the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.
Time frame: From the date of randomization to date of the first and second subsequent anticancer therapy or death, whichever came first, assessed up to 5 years.
Time to first subsequent treatment (TFST) Time to second Subsequent Treatment (TSST) in HER2 1+/2+/3+ population
Defined as the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.
Time frame: From the date of randomization to date of the first and second subsequent anticancer therapy or death, whichever came first, assessed up to 5 years.
Progression free survival 2 (PFS2) measured by investigator in HER2 1+/2+/3+ population
Defined by the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) or death.
Time frame: the time from treatment randomization to the earlier date of assessment of progression on the next anticancer therapy following study treatment or death by any cause, whichever came first, assessed up to 5 years.
OS in the HER2 IHC 2+/3+ population
Measured as the time from the date of randomization to the date of death
Time frame: the time from the date of inclusion until death due to any cause, assessed up to 5 years.
OS in the HER2 IHC 1+/2+/3+ population
Measured as the time from the date of randomization to the date of death
Time frame: the time from the date of inclusion until death due to any cause, assessed up to 5 years.
Response rate of subsequent therapies
Defined as the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
Time frame: From the start date of subsequent anticancer therapy until death due to any cause or study termination, assessed up to 5 years.
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