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).