Trastuzumab Deruxtecan (T-DXd): Tailoring Treatment and Companion Diagnostics (CDx) by Liquid Biopsy. DIAMOND STUDY
This is a prospective single-center pilot study phase II non randomized designed to explore the role of liquid biopsy in metastatic HER2-positive breast cancer patients treated with Trastuzumab deruxtecan (T-Dxd) as second line treatment according to international guidelines. All eligible patients to T-Dxd as second line treatment will receive T-Dxd intravenous at dose of 5,4 mg/kg every three weeks until progression disease or unacceptable toxicities. Subjects eligible to T-Dxd, who agree to participate in the study, will undergo serial blood samples for liquid biopsy (LB) until progression disease. The timing of blood drawing will be scheduled as follows: At each T-DXd administration for the first four cycles of T-Dxd (every three weeks). The next blood drawings will be done every three cycles of T-Dxd (every 9 weeks) until the thirteenth cycle. The next blood drawings will be done every six cycles of T-Dxd (every 18 weeks) until progression disease (documented by medical imaging) For all enrolled patients with available tumour tissue from primary diagnosis or last biopsy from recurrence, tissue samples will be requested for exploratory analysis.
• Must be competent and able to comprehend, sign, and date informed consent prior to any study specific procedures;
• Male or female subjects age ≥ 18 years;
• Subjects with histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy;
• Subjects must have confirmed, per local testing on most recent tumor tissue sample available, an HER2-positive expression, as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines (as defined in the 2013 American Society of Clinical Oncology (ASCO) recommendations for HER2 testing \[7\]) with any ER and/or PgR tumor status;
• Subjects must have received no more than one line of treatment including trastuzumab plus or not pertuzumab associated to taxane in the advanced/metastatic setting or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane;
• Documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy);
• Presence of at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (see Appendix A)
• Non measurable (evaluable) bone-only disease are eligible. Evaluable bone-only disease must include at least one lytic bone lesion or a mixed lytic-blastic bone lesion; blastic only metastases are not allowed. Subjects who have had prior radiation to bone must have at least one evaluable lesion in a non-irradiated area. Patients with lesions identified only on radionucleotide bone scan are not eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• Life expectancy \> 12 weeks;
• Subjects with clinically inactive brain metastases may be included in the study.
• Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrolment.
• LVEF ≥ 50% within 28 days before enrolment.
• Adequate organ and bone marrow function within 14 days before enrollment
• Adequate treatment washout period before enrolment
• Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP. Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause.
• Agree for periodically blood sample collection for liquid biopsy