A Study to Evaluate the Efficacy and Safety of GDC-9545 Combined with Palbociclib Compared with Letrozole Combined with Palbociclib in Patients with Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Phase 1

• Conditions: MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; First line of treatment for Estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer; MedDRA version: 23.0Level: LLTClassification code 10070577Term: Oestrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10083232Term: HER2 negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2020-000119-66-PL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-05
• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 978

Inclusion Criteria

– Age >= 18 years at time of signing Informed Consent Form
– For women who are premenopausal or perimenopausal or men: treatment with approved LHRH agonist therapy for the duration of study treatment
– Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
– Documented ER-positive tumor and HER2-negative tumor, assessed locally
– Confirmed availability of the most recently collected and representative tumor tissue specimen suitable for biomarker testing
– Patients who have bilateral breast cancers which are both ER positive and HER2 negative can be included in the study because the metastases are suitably targeted by the study treatments. If patients have bilateral tumors which are of different biomarker status, then proof of the ER and HER2 status of the metastases is required for study entry
– No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease
– Disease recurrence from early-stage breast cancer after standard adjuvant endocrine therapy meeting one of the following criteria:
• Received at least 24 months of AI treatment (i.e., anastrozole, letrozole, or exemestane) as part of their neoadjuvant/adjuvant therapy without disease progression during treatment and disease-free interval since the completion of AI treatment must be greater than 12 months
• Received at least 24 months of tamoxifen treatment as part of their neoadjuvant/adjuvant therapy without disease progression during treatment and disease-free interval since the completion of tamoxifen treatment must be greater than 12 months
• For patients who received both AI and tamoxifen as part of their neoadjuvant/adjuvant therapy, they must have received at least 24 consecutive months of either AI or tamoxifen without disease progression during treatment and disease-free interval since the completion of the last treatment must be greater than 12 months
– Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
– Eastern Cooperative Oncology Group Performance Status 0-1
– Adequate organ function
– Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade = 1 (except alopecia, Grade = 2 peripheral neuropathy or other toxicities not considered a safety risk for the patient per investigator's judgment)
– For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined in the protocol
– For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined in the protocol (and this includes the use of a condom to prevent the potential transfer of study medication or its metabolites to the partner in body fluids)
– Ability to comply with the study protocol, in the investigator's judgment
– Willing and able to use an electronic device for PRO data collection
– For patients enrolled in an extended China enrollment phase at NMPA-recognized sites: current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects

Exclusion Criteria

– Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor
– Prior treatment with a SERD
– Treatment with any investigational therapy within 28 days prior to study treatment
– Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
– Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
– History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I endometrial cancer
– Advanced, symptomatic, visceral spread that is at risk of life-threatening complications
– Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
– Active cardiac disease or history of cardiac dysfunction
– Active viral infection is clinically defined as requiring treatment with antiviral therapy or the presence of positive test results for hepatitis B (hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]) or HCV antibody. Patients are not required to have HBV, or HCV assessments at screening if these assessments have not been previously performed
– Serious infection requiring oral or IV antibiotics, or other clinically significant infection within 14 days prior to randomization. Patients who fully recovered from serious or clinically significant infections at least 14 days prior to screening are eligible
– For patients who have been successfully treated for viral hepatitis, the possibility of re activation of the virus or reinfection with viral hepatitis should be considered by the Investigator and the overall potential benefits associated with study treatment for the patient should be deemed to exceed the overall risks.
– Known HIV infection
– Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
– Pregnant or breastfeeding

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified