None listed
Conditions
Interventions
Drug : * Subjects will be randomly assigned 1:1 to one of two groups.
1) Arm A: Trastuzumab deruxtecan (T-Dxd) ± Bevacizumab
- T-Dxd 5.4 mg/kg administered intravenously every 3 weeks until disease p
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 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. 2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements. 3. Has HER2 expression per 2016 ASCO-CAP gastric cancer IHC scoring (3+/2+/1+) guidelines by local tests. 4. Availability of tumor tissue for translational research: A formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at least 20 slides (unstained, freshly cut, serial sections) must be submitted. 5. Histologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent. 6. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 7. Radiologically confirmed/documented disease progression while on PARP inhibitor therapy in either first or second-line maintenance setting Note: Documentation of disease progression must be within 180 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed. a) Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed. b) 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. c) Progression on second-line maintenance PARP inhibitor: Participants are not allowed any additional systemic anticancer treatment before study entry. 8. Patient with measurable disease according RECIST 1.1 criteria. 9. LVEF =50% within 28 days before randomization. 10. Patient has adequate organ function, defined as follows: a) Absolute neutrophil count = 1,500 cells/µL b) Platelets = 100,000 cells/µL c) Hemoglobin = 9 g/dL or = 5.6 mmol/L d) Serum creatinine = 1.5× upper limit of normal (ULN) or calculated creatinine clearance = 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN e) Total bilirubin = 1.5× ULN (= 2.0 x ULN in patients with known Gilbert’s syndrome) or direct bilirubin = 1× ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5× ULN unless liver metastases are present, in which case they must be = 5× ULN g) International normalized ratio or prothrombin time (PT) =1.5× ULN and activated partial thromboplastin time =1.5× ULN. Patients receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants. 11. Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of nonchildbearing potential. Nonchildbearing potential is defined as follows: a) Patient is = 45 years of age and has not had menses for > 1 year. b) A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrhoeic for < 2 years without a hysterectomy and oophorectomy. c) Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation: - Documented hysterectomy or bilateral oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, MRI, or CT scan. - Tubal ligation must be
Exclusion criteria
Exclusion criteria: 1. Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the last platinum administration in the second-line setting. 2. History of additional malignancy within 3 years before the date of enrolment. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor, is considered cured with minimal risk of recurrence within 3 years. 3. Patient has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy) within 21 days or < 5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter. Note: The washout period for radiation therapy is as follows: = 4 weeks for palliative stereotactic radiation to chest and =2 weeks palliative stereotactic radiation therapy to other anatomic areas. 4. Patient has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability. 5. Active and/or uncontrolled infection. The following exceptions apply: a) 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. b) 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. c) 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. 6. Patient has not recovered (i.e., to Grade = 1 or to baseline) from cytotoxic therapy-induced adverse events (AEs). Note: Patients with Grade = 2 neuropathy, Grade = 2 alopecia, or Grade = 2 fatigue are an exception to this criterion and may qualify for the study. 7. Patient has not recovered adequately from AEs or complications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) in HER2 IHC 1+/2+/3+ population | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) in HER2 IHC 2+/3+ population;Objective Response Rate (ORR) by investigator in HER2 2+/3+ population;Objective Response Rate (ORR) by investigator in HER2 1+/2+/3+ population;Disease control rate (DCR) by investigator in HER2 2+/3+ population;Disease control rate (DCR) by investigator in HER2 1+/2+/3+ population;Clinical benefit rate (CBR) by investigator in HER2 2+/3+ population;Clinical benefit rate (CBR) by investigator in HER2 1+/2+/3+ population;Duration of Response Rate (DoR) by investigator in HER2 2+/3+ population;Duration of Response Rate (DoR) by investigator in HER2 1+/2+/3+ population;Safety endpoints;Time to first subsequent treatment (TFST) Time to second Subsequent Treatment (TSST) in HER2 2+/3+ population;Time to first subsequent treatment (TFST) Time to second Subsequent Treatment (TSST) in HER2 1+/2+/3+ population;Progression free survival 2 (PFS2) measured by investigator in HER2 2+/3+ population;Progression free survival 2 (PFS2) measured by investigator in HER2 1+/2+/3+ population;OS in the HER2 IHC 2+/3+ population;OS in the HER2 IHC 1+/2+/3+ population;Response rate of subsequent therapies;Biomarker outcomes | — |
Countries
Korea, Republic of
Contacts
Public ContactEunyeong Yang
Yonsei University Health System, Severance Hospital
Outcome results
None listed