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
1. Adults ≥18 years of age on the day of signing the Informed Consent Form. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed.
Progression on first-line maintenance PARP inhibitor: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry (note: treatment-free interval on platinum rechallenge must be > 6 months, with documented disease progression prior to study entry.
Progression on second-line maintenance PARP inhibitor: Participants are not allowed any additional systemic anticancer treatment before study entry.
Participants with HIV infection are eligible if followings are met: a. CD4+ T-cell count ≥350 cells/mm3 at the time of screening, b. Virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) at the time of screening and for at least 12 weeks before screening, c. No AIDS-defining opportunistic infections or conditions within the past 12 months, d. On stable ART regimen, without changes in drugs or dose modification, for at least 4 weeks before trial entry (Day 1) and agree to continue ART throughout the trial.
Participants with evidence of chronic HBV infection are eligible if the followings are met: a. the HBV viral load is <2000 IU/mL b. start or maintain antiviral treatment, if clinically indicated as per the investigator. c. they have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HBV infection.
Participants with a history of HCV infection are eligible if History of hepatitis C infection eligible if the HCV viral load is below the level of detection in the absence of antiviral therapy during the previous 4 weeks and if they Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HCV infection.
QT interval corrected with Fridericia's formula interval >470 ms (average of triplicate determinations).
Parallel
Trastzumab Deruxtecan
DrugTrastzumab deruxtecan will be administrated via intravenous, every 3 weeks.
Bevacizumab
DrugBevacizumab 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
Platinum Based Chemotherapy
Drug\*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
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.
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
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
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
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.
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