Locally advanced or metastatic breast cancer. MedDRA version: 21.1 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: S64315
Product Code: S64315 (also referred as MIK665)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: S64315
Current Sponsor code: S64315
Other descriptiv
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In Arm 1: S64315 + paclitaxel -Histologically confirmed locally advanced or metastatic TNBC or HR+/Her2- (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by immunochemistry), FISH BC (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2): TNBC: no more than 2 prior chemotherapeutic regimens in the locally advanced or metastatic setting HR+/Her2-: no more than 2 prior chemotherapeutic regimens and no more than 1 prior PI3K inhibitor (PIKi) in the locally advanced or metastatic setting In Arm 2: S64315 + eribulin -Histologically confirmed locally advanced or metastatic TNBC or HR+/Her2- BC (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by immunochemistry), FISH (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2): TNBC: no more than 2 prior chemotherapeutic regimens in the locally advanced or metastatic setting HR+/Her2-: no more than 2 prior chemotherapeutic regimens and no more than 1 prior PI3Ki in the locally advanced or metastatic setting -No prior exposure to eribulin in the adjuvant, neoadjuvant or metastatic setting In Arm 3: S64315 + fulvestrant -Histologically confirmed locally advanced or metastatic HR+/Her2- BC: (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by mmunochemistry), FISH (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2) No more than two prior lines of hormonal therapy in the locally advanced or metastatic setting Prior treatment with CDK4/6 inhibitor (CDK4/6i) is permitted Prior treatment with PI3K inhibitor (PI3Ki) is permitted Patients for whom endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at the time of entry into the study, as per national or local treatment guidelines -Post-menopausal women For all patients: -Patient must have at least one measurable lesion, as defined by revised RECIST v1.1, 2009 -Estimated life expectancy = 12 weeks -Eastern Cooperative Oncology Group (ECOG) performance status = 1 -Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP administration. -Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration. -Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration. -Serum CK/CPK = 2.5 ULN 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 for this age range 174 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 116
Exclusion criteria
Exclusion criteria: -Only for Arm 1 and 2: Pregnant and lactating women -Patients who have not recovered from toxicity of previous anticancer therapy, including grade = 2 non-haematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.00), prior to the first IMP administration Certain toxicities will not be considered in this category (e.g. alopecia) -Severe or uncontrolled active acute or chronic infection -Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active viral or other hepatitis or cirrhosis -Medical history of acute or chronic pancreatitis -Unresolved diarrhoea = CTCAE Grade 2 or presence of medical condition associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease) -Clinically significant cardiac dysfunction (including NYHA Class = II heart failure, left ventricular ejection fraction (LVEF) 150 mmHg or diastolic blood pressure > 95 mmHg despite treatment) -Acute coronary syndrome including unstable angina pectoris (anginal symptoms at rest), new onset angina, acute myocardial infarction, coronary artery bypass graft (CABG) within 3 months prior to starting study treatment -Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, atrial fibrillation), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) -Congenital or substance-induced long QT defined as QTc interval > 450 ms for males and > 470 ms for females according to Frederica’s formula -Troponin (I or T) > ULN -Patients with coagulopathy that will increase the risk of bleeding complications according to investigator’s judgment (e.g. disseminated intravascular coagulation) -Known hypersensitivity to paclitaxel /eribulin /fulvestrant or S65315 including excipients of the liposomal vehicle, eggs or soybean -Only for Arm 1 and Arm 2: Evidence of peripheral neuropathy = CTCAE grade 2 -Major surgery (involving a risk to the life of the patient) within 4 weeks prior to the first dose of IMP, or patients who have not recovered from side effects of the surgery -Any radiotherapy within 2 weeks before the first dose of IMP (except for palliative radiotherapy at localised lesions)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I objective: -To determine the safety profile (including Dose Limiting Toxicities, Maximum Tolerated Doses), tolerability and the Recommended Doses for Expansion (RDEs) of S64315 in combination with various standard treatments including hormonal and cytotoxic agents according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Phase II objective: -To evaluate the Objective Response Rate (ORR) of S64315 in combination with various standard treatments including hormonal and cytotoxic agents;Secondary Objective: Phase I objectives: -To determine the pharmacokinetics (PK) profile in plasma of S64315 in combination with various standard treatments including hormonal and cytotoxic agents -To investigate any preliminary antitumor activity of these combinations Phase II objectives -To assess the anti-tumour activity according to the Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1, 2009) in terms of: Response duration (RD) Overall survival (OS) Progression Free Survival (PFS) Best Overall Response (BOR) Disease Control Rate (DCR) -To assess the safety and tolerability of S64315 in combination with various standard treatments including hormonal and cytotoxic agents, at RDEs, according to NCI-CTCAE v5.0 -To assess the PK profile in plasma of S64315 in combination with various standard treatments including hormonal and cytotoxic agents;Primary end point(s): Phase 1: -Incidence of DLTs during the first cycle of treatment with S64315 combined with various standard treatments including hormonal and cytotoxic agents -Incidence and severity of AEs and SAEs will be evaluated according: Laboratory tests: haematology with differential, blood biochemistry, thyroid function, coagulation and urinary analysis Vital signs and performance status ECG parameters to be centrally read, cardiac function assessment LVEF assessed by echocardiography or MUGA scan -Dose interruptions, reductions and dose intensit | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Blood samples for PK: Arm 1 and arm 2: C1D1, C1D2, C1D3, C1D8, C1D9 and C1D10. Arm 3: C1D1, C1D2, C1D3, C1D8, C1D15. Tumor measurement by RECIST v1.1: at the end of every two cycles;Secondary end point(s): Phase 1: -PK parameters of S64315 administered in combination with various standard treatments including hormonal and cytotoxic agents in plasma -Tumor response assessed by RECIST v1.1 (ORR, BOR, DCR) Phase 2: -RD is derived for those patients with objective PR or CR and is defined from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the date of progression or death (whatever the reason of death), whichever occurs first -OS is defined as the time from the study enrolment to death from any cause (the follow-up period will be 12 months) -PFS is defined as the time from the study enrolment date until the date of the investigator-assessed radiological disease progression according to RECIST v1.1 or death due to any cause -BOR is defined as the best response recorded from the start of the study treatment until the disease progression/recurrence -DCR is defined as the percentage of patients who achieve best response: Complete response (disappearance of all target lesions), Partial response (=30% decrease in the sum of the longest diameter of target lesions) Or stable disease =24 weeks based on RECIST v.1.1 -Safety and tolerability of S64315 in combination with various standard treatments including hormonal and cytotoxic agents assessed by: Incidence and severity of AEs and SAEs Laboratory tests (haematology, haemolysis biochemistry, urinary analysis and pregnancy test) Vital signs and body weight Physical examination and performance status ECG parameters Dose interruptions, dose reductions and dose intensity -PK parameters of S64315 in combination with various standard treatments including hormonal and cytotoxic agents | — |
Countries
Australia, France, Hungary, Italy, Spain
Contacts
Public ContactIlaria Fasciani
Laboratorios Servier S.L.
Outcome results
None listed