RIBOCICLIB for Hormone receptor-positive breast cancer|HR+/HER2- advanced breast cancer

Inclusion criteria

• {"criterion_text":"-Patient must be capable of understanding the purpose of the Study and have signed the written informed consent form (ICF) prior to beginning specific protocol procedures.\n-Evidence of measurable disease as per RECIST v.1.1, or nonmeasurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.\n-For patients receiving tamoxifen or toremifene, a washout period of 35 days (5 half-lives) prior to randomization is required\n-Patients must agree to provide and have available a FFPE tissue biopsy sample taken at the time of presentation with recurrent or metastatic disease. If this is not available, archived primary breast cancer specimen may be submitted\n-Adequate bone marrow and organ function: - Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within seven days before treatment initiation): White blood cell (WBC) count > 3.0 x 10^9 /L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L; platelet count ≥ 100.0 x10^9 and hemoglobin ≥ 9.0 g/dL. - Hepatic: Serum albumin ≥ 2.5 g/dL; total serum bilirubin < 1.5 x upper limit of normal (ULN) except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN; alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 3 x ULN in patients with liver and/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases); international normalized ratio (INR) < 1.5. Prothrombin time (PT) or Prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN, factor Xa inhibitors, or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator from product safety requirements (PSR). - Renal: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault equation.\n-Patient must be available and willing to participate in the treatment and follow-up assessments as required.\n-Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 4 weeks after the last dose of Study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period. Non-sterilized male partners of heterosexually active females of childbearing potential participants must use a male condom from the time of enrollment of their female partner, throughout their participation in the Study, and until 4 weeks after their female partner’s last dose of Study intervention.\n-Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable highly effective method of contraception from the time of screening until 21 days after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period. Female partners of childbearing potential of male participants must agree to use one highly effective method of contraception from the time of screening until 4 weeks after the last dose of Study treatments.\n-ECOG performance status of 0-1.\n-Minimum life expectancy of ≥ 6 months.\n-Female or male patients ≥ 18 years of age at the time of signing ICF.\n-Pre- or peri-menopausal women or men. are eligible if treated with a Luteinizing hormone-releasing hormone (LHRH) analogue. Treatment with a LHRH is recommended for at least 28 days prior to study treatment; if shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH] must be confirmed analytically prior to Study enrollment.\n-Post-menopausal women, defined by any of the following criteria: o Cessation of menses for at least 12 consecutive months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. o Documented bilateral surgical oophorectomy.\n-Documented histologically confirmed HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as per local assessment on the most recent analyzed biopsy. Therefore, tumors must be: o HR+ defined as ≥ 10% of tumor cells stain positive for estrogen receptor (ER) on immunohistochemistry (IHC), and HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridization (ISH).\n-Unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n-Patients must have received at least five years of adjuvant endocrine therapy, including at least two years of an AI (capped to 30% patients with treatment-free interval [TFI] ≥ 12 months.\n-Patients must have: - Radiological evidence of progression while on, or within 12 months of the end of (neo)adjuvant endocrine therapy (secondary endocrine resistance criteria), or - Radiological evidence of progression more than 12 months of the end of (neo)adjuvant endocrine therapy (endocrine sensitive criteria).\n-Patients receiving a CDK4/6 inhibitor-based therapy in the (neo)adjuvant setting are eligible if disease progression is confirmed more than 12 months following CDK4/6 inhibitor treatment completion in this scenario."}

Exclusion criteria

• {"criterion_text":"-Formal contraindication to endocrine therapy defined as visceral crisis and/or rapidly or symptomatic progressive visceral disease.\n-Current participation in another therapeutic clinical trial.\n-Has previously been treated with any SERD, including camizestrant, experimental ETs or fulvestrant.\n-Prior systemic therapy for advanced disease.\n-Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.\n-History of another primary malignancy except for the following: a. Malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of Study treatment, and of very low potential risk for recurrence. b. Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease. c. Other exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. Note: For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.\n-Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances. Note: Ribociclib is contraindicated for patients with hypersensitivity/allergy to peanut or soya.\n-History of malabsorption syndrome or other condition that would interfere with enteral absorption (ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass) or results in the inability or unwillingness to swallow pills.\n-Palliative radiotherapy with a limited field of radiation within two weeks or with wide field of radiation or radiation to more than 30% of the bone marrow within four weeks prior to Study enrollment.\n-Major surgical procedure or significant traumatic injury within 14 days before Study enrollment or anticipation of need for major surgery within the course of the Study treatment.\n-Cardiac symptoms, procedures, or test results as follows: Unexplained syncope (within the last six months prior to Study enrollment), or ongoing symptomatic hypotension, or ongoing asymptomatic hypotension with blood pressure systolic < 90 mmHg. Second- and third-degree heart block, or clinically significant sinus pause or sinoatrial block. Patients with pacemakers or medically controlled atrial fibrillation are not excluded. Factors that increase the risk of QTc prolongation or the risk of arrhythmic events such as symptomatic heart failure, congenital long QT syndrome, immediate family history of long QT syndrome, unexplained sudden death < 40 years of age, hypertrophic cardiomyopathy and clinically significant stenotic valve disease. Known left ventricular ejection fraction (LVEF) <50% with heart failure NYHA Grade ≥ 2. Untreated electrolyte abnormalities with potential QT-prolonging effect including altered levels of serum/plasma potassium, magnesium, and calcium. Note: Correction of electrolyte abnormalities to within normal ranges can be performed during the screening period. Mean resting QTcF interval > 450 ms, obtained from triplicate-ECG performed at screening. Resting heart rate consistently 50-90 bpm. Repeat measurements are permitted during the screening period. Uncontrolled hypertension. Blood pressure systolic > 160 and diastolic > 90 mmHg despite optimal medical management. Note: Hypertensive patients may be eligible, but blood pressure must be adequately controlled at baseline. Experience of any of the following procedures or conditions in the preceding six months: coronary artery bypass graft, angioplasty, vascular stent, any other structural heart disease interventions (e.g., cardiac valve repair or replacement surgery or transcatheter valve treatment), severe aortic regurgitation (Grades 3 and 4), myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack.\n-Known abnormalities in coagulation such as bleeding diathesis, or any history of coagulopathy within six months before Study enrollment, including history of deep vein thrombosis or pulmonary embolism.\n-Patients treated: Within 2 weeks prior to first dose: medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic range (e.g. warfarin/phenytoin) or who have not fully recovered from side effects of such treatment. With medications that are known to prolong the QT interval and have a known risk of Torsades de Pointes.\n-Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.\n-Current known infection with human immunodeficiency virus (HIV) detectable viral load, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.\n-Any other active uncontrolled infection at the time of screening.\n-Known substance abuse or any other concurrent severe and/or uncontrolled psychiatric or medical condition that would, in the Investigator’s judgment, contraindicate patient participation."}

Primary endpoints

• {"endpoint_text":"-PFS, defined as the time from the date of the first dose until disease progression or death from any cause, whichever occurs first (compared to PFS of the historical control arm), as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Defined as time from first dose to disease progression or death; determined locally by investigator using RECIST v1.1; compared to PFS of historical control arm."}

Secondary endpoints

• {"endpoint_text":"-ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Rate of patients with CR or PR determined locally by investigator using RECIST v1.1."}
• {"endpoint_text":"-CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Rate of patients with CR or PR or stable disease ≥24 weeks per RECIST v1.1, determined locally."}
• {"endpoint_text":"-TTR, defined as the period from treatment initiation to the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Time from treatment start to first objective tumor response (≥30% tumor shrinkage) per RECIST v1.1, determined locally."}
• {"endpoint_text":"-DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Time from first documented objective response to progression or death per RECIST v1.1, determined locally."}
• {"endpoint_text":"-Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Percent change from baseline in target lesion size per RECIST v1.1, determined locally."}
• {"endpoint_text":"-TTSLC, defined as the period from treatment initiation to the subsequent line of chemotherapy as determined locally by the investigator.","definition_or_measurement_approach":"Time from treatment initiation to start of subsequent chemotherapy, determined locally by investigator."}
• {"endpoint_text":"-Changes from baseline in the EORTC quality of life (QLQ-C30), the BC-specific (QLQ-BR42), PRO-CTCAE, Global Items (PGIS, PGIC, PGI-TT), and EQ-5D-5L questionnaires.","definition_or_measurement_approach":"Change from baseline in listed patient-reported outcome questionnaires."}
• {"endpoint_text":"-Safety and tolerability as per NCI-CTCAE v.5.0.","definition_or_measurement_approach":"Adverse events graded using NCI CTCAE v5.0."}
• {"endpoint_text":"-Efficacy endpoints for all patients as compared to efficacy endpoints obtained from real world database.","definition_or_measurement_approach":"Comparison of study efficacy endpoints to those derived from a real-world database (methodology not further specified in provided data)."}
• {"endpoint_text":"-Kaplan Meier estimates of PFS and hazard ratio of patients with ESR1 mutation detected versus non-detected","definition_or_measurement_approach":"Kaplan-Meier PFS estimates and HR comparing ESR1 mutation positive vs negative patients."}
• {"endpoint_text":"-Kaplan-Meier estimates of OS and hazard ratio of patients with ESR1 mutation detected versus non-detected.","definition_or_measurement_approach":"Kaplan-Meier OS estimates and HR comparing ESR1 mutation positive vs negative patients."}
• {"endpoint_text":"-Mutation profiling, copy number variability, gene expression, multiplex assays, proteomic analyses, digital pathology, immunohistochemistry, taxonomic or functional analyses may be performed in blood and tumor tissue samples of all patients to determine their potential relationship with clinical outcomes, safety, and/or tolerability profile.","definition_or_measurement_approach":"Exploratory molecular and pathology analyses on blood and tumor samples to assess associations with outcomes, safety, and tolerability (methods as listed)."}
• {"endpoint_text":"-Association of treatment efficacy and/or safety outcomes in all patients with radiological imaging biomarkers","definition_or_measurement_approach":"Assessment of associations between imaging biomarkers and efficacy/safety outcomes (detailed methods not provided)."}

Germany

Earliest CTIS Part Ii Submission Date

24-11-2025

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

29

Number Of Sites

4

Number Of Participants

27

Spain

Earliest CTIS Part Ii Submission Date

11-11-2025

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

80

Number Of Sites

20

Number Of Participants

104

Primary sponsor

Full Name

Medica Scientia Innovation Research S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"ASTRAZENECA FARMACÉUTICA SPAIN, S.A.","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Novartis Pharma AG","duties_or_roles":"Monetary support","organisation_type":""}