A phase 2 study to evaluate the efficacy and safety of Trastuzumab Deruxtecan for molecular progression based on ctDNA analysis during CDK4/6 inhibitor and endocrine treatment in patients with HR-positive and HER2-low metastatic breast cancer (JBCRG-M11 ( CAERUS trial )
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1. Performance status is 0 or 1 according to the ECOG criteria.
2. Estrogen receptor positive or progesterone receptor positive breast cancer has been confirmed.
3. HER2 low status has been confirmed by an approved companion diagnostic test.
4. Prior to initiation of therapy with a CDK4 and 6 inhibitor in combination with endocrine therapy, the presence of distant metastatic disease meeting at least one of the following criteria has been confirmed. This corresponds to metastatic breast cancer. Visceral metastasis. Two or more lymph node metastases. Two or more bone metastases. Patients are eligible if the above metastatic lesions were confirmed by imaging before initiation of therapy with a CDK4 and 6 inhibitor in combination with endocrine therapy, even if the lesions are no longer detectable at the time of primary registration due to treatment response.
5. The patient is currently receiving therapy with a CDK4 and 6 inhibitor in combination with endocrine therapy as first line treatment or second line treatment for metastatic breast cancer. Definitions of eligible first line and second line therapies are as follows.
a. De novo Stage IV breast cancer. First line therapy is defined as the first systemic drug therapy initiated. Second line therapy is defined as the second systemic drug therapy initiated after endocrine monotherapy was used as the first systemic therapy.
b. Recurrence during or within 12 months after completion of adjuvant endocrine therapy. First line therapy is not applicable. Second line therapy is defined as the first systemic drug therapy after recurrence.
c. Recurrence occurring 12 months or more after completion of adjuvant endocrine therapy. First line therapy is defined as the first systemic drug therapy after recurrence. Second line therapy is defined as the second systemic drug therapy initiated after endocrine monotherapy was used as the first systemic therapy after recurrence.
6. Therapy with a CDK4 and 6 inhibitor in combination with endocrine therapy has been continued without disease progression for at least 3 months and less than 15 months, and all of the following conditions are met.
a. The CDK4 and 6 inhibitor is abemaciclib or palbociclib. If abemaciclib or palbociclib was administered as perioperative therapy, at least 12 months must have elapsed between the last dose and disease recurrence.
b. The endocrine therapy is either an aromatase inhibitor, including anastrozole or letrozole, or fulvestrant, and must be an agent for which resistance has not previously been confirmed. Resistance is defined as recurrence during perioperative therapy or within 12 months after the last dose, or disease progression during treatment for metastatic breast cancer. Premenopausal patients must additionally receive a luteinizing hormone releasing hormone agonist.
c. All study drugs are administered in accordance with the approved dosage and administration described in the package insert.
7. The patient has not received cytotoxic chemotherapy for the treatment of metastatic breast cancer. Molecular targeted agents and endocrine therapy are excluded.
1. The patient has central nervous system metastases, regardless of whether the metastases are active or inactive.
2. The patient has multiple primary malignancies.
3. The patient has myocardial infarction or symptomatic congestive heart failure classified as New York Heart Association Class II to Class IV, or has a history of any of these conditions within 6 months prior to primary registration.
4. The patient has non infectious interstitial lung disease or pneumonitis requiring steroid treatment, or has a history of these conditions.
5. The patient is pregnant, breastfeeding, or planning to become pregnant.
18age old over
No limit
Female
Hormone receptor-positive and HER2-low metastatic breast cancer
Investigational Drug:Trastuzumab deruxtecan (T-DXd)
Dosage and Administration
Treatment Period (Step 2):Trastuzumab deruxtecan will be administered intravenously every 3 weeks (2 days before or after) for up to 24 weeks, with an infusion duration of 90 minutes (10 minutes before or after).
The initial dose will be 5.4 mg/kg.
Continuation Treatment Period (Step 3)
T-DXd Continuation Group:Following the treatment period, the investigational product will be administered by intravenous infusion every 3 weeks (2 days before or after) for 24 weeks, with an infusion duration of 90 minutes (10 minutes before or after). The dose will be maintained at the same level as the final dose administered in Step 2 (treatment period).
CDK4/6i + ET Resumption Group:The CDK4/6 inhibitor plus endocrine therapy (CDK4/6i + ET) administered during the pre-observation period will be resumed.
In principle, the regimen (type of agents, dosage, and administration) will be the same as that used at the end of the pre-observation period.
Proportion of patients achieving molecular complete response (mCR) at 24 weeks after registration
Efficacy Endpoints:
Time to molecular complete response, Progression free survival (PFS), Overall survival (OS), Objective response rate (ORR), Molecular objective response rate (mORR), Proportion of patients with molecular progressive disease (mPD) and time to molecular progressive disease, Second progression free survival (PFS2), Tumor markers
Safety Endpoints:
Adverse events, Clinical laboratory tests, Physical examination, Vital signs, Performance status (ECOG PS), Electrocardiogram, Cardiac assessments
none
Daiichi Sankyo Company, Limited
Not applicable
The Institutional Review Board, The University of Osaka Hospital
