g1t48, an oral serd, alone and in combination with palbociclib in er-positive, her2-negative advanced breast cancer

Conditions: Carcinoma, Ductal, Breast; Breast Cancer Female; Breast Neoplasm; Breast Cancer; Metastatic Breast Cancer; Advanced Breast Cancer; Stage IV Breast Cancer

Summary: this is a study to investigate the potential clinical benefit of g1t48 as an oral selective estrogen receptor degrader (serd) alone and in combination with palbociclib, a cyclin dependent kinase 4/6 (cdk 4/6) inhibitor, in patients with estrogen receptor-positive, her2-negative metastatic breast cancer. the study is an open-label design, consisting of 3 parts: dose-finding portion including food effect (part 1), g1t48 monotherapy expansion portion (part 2), and g1t48 in combination with palbociclib expansion portion (part 3). all parts include 3 study phases: screening phase, treatment phase, and survival follow-up phase. the treatment phase begins on the day of first dose with study treatment and completes at the post-treatment visit. approximately, 184 patients may be enrolled in the study.


Eligibility criteria:
inclusion criteria: * for part 1, postmenopausal women only * for parts 2 and 3, any menopausal status * confirmed diagnosis of er-positive, her2-negative advanced breast cancer, not amenable to curative therapy * for part 1, prior treatment with less than 4 prior lines of chemotherapy * for part 2, prior treatment with less than 2 prior line of chemotherapy * for part 3, prior treatment with no more than 1 prior line of chemotherapy * for parts 1 and 2, prior treatment with less than 4 prior endocrine therapies for metastatic breast cancer * for part 3, prior treatment with no more than 1 prior line of endocrine therapies for metastatic breast cancer * for parts 1 and 2, patients must satisfy 1 of the following criteria for prior therapy: * progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor * progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer * for part 3, patients must satisfy 1 of the following criteria for prior therapy: * received ≥ 24 months of endocrine therapy in the adjuvant setting prior to recurrence or progression * received ≥ 6 months of endocrine therapy in the advanced/metastatic setting prior to progression * for part 1, evaluable or measurable disease * for parts 2 and 3, evaluable (approximately 25%) or measurable disease (approximately 75%) as defined by recist, version 1.1 including bone-only disease * ecog performance status 0 to 1 * adequate organ function exclusion criteria: * for part 3, prior treatment with cdk4/6 inhibitor, investigational oral serds or sercas in any setting * active uncontrolled/symptomatic cns metastases, carcinomatous meningitis, or leptomeningeal disease * anticancer therapy within 14 days of first g1t48 dose or within 28 days for antibody-based therapy * concurrent radiotherapy, radiotherapy within 14 days of first g1t48 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to \> 25% of bone marrow * prior hematopoietic stem cell or bone marrow transplantation

Keywords: breast cancer oral serd serd her2-negative er-positive er+ her2- her2 -ve er +ve cdk 4/6 inhibitor rintodestrant g1t48