A Phase I/II, open-label, multi-center trial of [177Lu]Lu-NeoB in combination with capecitabine in adult patients with gastrin releasing peptide receptor positive, estrogen receptor-positive, human epidermal growth receptor-2 negative metastatic breast cancer after progression on previous endocrine therapy in combination with CDK4/6 inhibitor
- Conditions
- Breast CancerMedDRA version: 20.1Level: PTClassification code: 10055113Term: Breast cancer metastatic Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506717-21-00
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
Participant is female or male adult = 18 years old at the time of informed consent(s), For Phase I part only : Female participant must be in postmenopausal status at the time of starting study treatment, as defined in Section 5.1 For Phase II part only Female participant is post-menopausal as per criteria above at the time of starting study treatment. Female participant is pre/peri-menopausal at the time of starting study treatment, as defined in Section 5.1, Participant has a histologically and/or cytologically documented diagnosis of ER+ breast cancer (ER expression >10% of tumor cell nuclei stain (regardless of PgR expression) (based on the most recently analyzed tissue sample tested by a local laboratory)., Participant has HER2- breast cancer defined as a negative in situ hybridization test (ISH) or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH (e.g., FISH, CISH, or SISH) (based on the most recently analyzed tissue sample tested by a local laboratory) is required., Participant received no more than three prior endocrine therapy/ies (single agent or in combination with targeted therapy) regimen/s in the metastatic setting of which at least one included endocrine therapy in combination with a CDK4/6i. In addition: - In case of confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the participant may also have received a PARP inhibitor-based therapy. - In case of HER2-low breast cancer, the participant may also have received Enhertu®. Note: disease progression while on adjuvant ET (with or without CDK4/6i) or within 12 months of completing adjuvant endocrine therapy (with or without CDK4/6i), will be considered a line of therapy., Participant has metastatic breast cancer with radiologically confirmed progression of disease after the most recent therapy, Participant must have measurable disease, i.e., at least one measurable lesion as per RECIST 1.1. (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation) as per local assessment. Note: If only lytic bone lesions are present, they must have at least one lesion with a soft tissue component that can be evaluated by CT or MRI and meets the definition of measurability as per RECIST 1.1 criteria (participants with only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation)., Participant has at least one target lesion [as per RECIST 1.1 and based on the baseline contrast-enhanced CT (or MRI)] with [68Ga]Ga-NeoB uptake above the liver at PET/CT or PET/MRI, as per local reading. In addition: Participant with liver or lung disease involvement must show [68Ga]Ga-NeoB uptake above the liver as follows: If there is liver disease involvement (in the absence of lung involvement), in = 50% of all CT measurable liver lesions (RECIST 1.1) If there is lung disease involvement (in the absence of liver involvement), in = 50% of all CT measurable lung lesions (RECIST 1.1) Participants with both liver and lung disease involvement must show [68Ga]Ga-NeoB uptake above the liver in = 50% of all CT measurable lesions either in liver or lung (RECIST 1.1) and in at least one measurable lesion in the remaining organ (lung or liver), Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1., Participant has adequate bone
Participant with symptomatic visceral disease or any disease burden that are at risk of life-threatening complications as per the investigator’s judgment., Sexually active male participants unwilling to: remain abstinent (refrain from sexual intercourse) or use a condom, while taking study treatment and for at least 4 months after the last administration of [177Lu]Lu-NeoB, or 3 months after the last dose of capecitabine (or as per locally prescribing information) whichever is longer, in addition to the highly effective method used by the partner who is a female of child-bearing potential., For Phase II part only ·Pregnant or breast-feeding women ·Women of childbearing potential, Participant has received prior treatment with chemotherapy in the metastatic setting (allowed in neoadjuvant/ adjuvant setting, unless progression or recurrence occurred during or within 12 months after completion of adjuvant chemotherapy)., Participant has received prior treatment with capecitabine, Participant has inflammatory breast cancer at screening., Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol, History or current diagnosis of impaired cardiac function, clinically significant cardiac disease or ECG abnormalities, Participant is currently receiving brivudine which cannot be discontinued at least 4-week prior to start of capecitabine therapy., Participant is currently receiving NEP inhibitors (i.e., Entresto®) and images for dosimetry assessments cannot be acquired for this participant as per Section 8.7.3 of the protocol., Participant with known deficiency or family history of deficiency of dihydropyrimidine dehydrogenase.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method