BMS CA209-7FL: A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
cancer du sein ER positif et HER2 négatif
nivolumab ou placebo en association avec une chimiothérapie avant l’opération, puis nivolumab ou placebo en association avec une hormonothérapie après l’opération
carcinome du sein invasif unilatéral confirmé histologiquement
Rue du Bugnon 46
+41 21 314 79 05
Primary objective :
Cette étude a pour but de déterminer l’efficacité, la sécurité et la tolérance du nivolumab (Opdivo) en association avec une chimiothérapie et du nivolumab en association avec une hormonothérapie chez des participants à qui l’on vient de diagnostiquer un cancer du sein à haut risque de type ER positif (récepteurs d’œstrogènes positifs) et HER2 négatif (récepteur 2 du facteur de croissance épidermique humain négatif).
Inclusion criteria :
- Participants must have histologically confirmed unilateral invasive breast carcinoma
- Participants must have ER+, HER2-BC
- Participants must be deemed eligible for neoadjuvant chemotherapy.
- Participants must be deemed eligible for surgery and must agree to undergo surgery after the completion of neoadjuvant therapy.
- Participants must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1
- Participants must have the ability to swallow oral medication.
- Participants must agree to provide tumor tissue at baseline (collected ≤ 60 days prior to enrollment) and at Surgery.
- Re-enrollment: This study permits the re-enrollment of a participant that has discontinued the study as a pretreatment failure (ie, participant has not been randomized).
- Randomized participants: PD-L1 status, ER status, and ER expression level percentage from the central laboratory must be provided to IRT prior to randomization.
- Males and females, agedat least 18yearsor age of majority.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
- Female participants must agree to use effective contraception.
- WOCBP must agree to follow instructions for method(s) of contraception.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception and fetal protection. In addition, male participants must be willing to refrain from sperm donation during this time.
- Male participants must agree to use contraception and refrain from donating sperm during the Treatment Period.
Exclusion criteria :
- Women who are breastfeeding.
- Participants who are pregnant or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months for participants who receive cyclophosphamide, or 6 months for participants who donot receive cyclophosphamide, after the last dose of studytreatment.
- The following BC characteristics: i) History of ipsilateral invasive BC,regardless of treatment,ipsilateral ductal carcinoma in situ treated with radiation, or contralateral invasive BC, at any time. ii) Definitive clinical or radiologic evidence of metastatic disease. iii) Inoperable BC. iv) Multicentric BC (the presence of >1 tumor in different quadrants of the breast). v) Bilateral invasive BC. vi) Any of the following clinical lymph node stagingbased on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c(refer to Appendix9[Staging Criteria]). vii) History of DCIS, unless a complete remission was achieved at least 2 years prior to study start and no additional therapy is required or anticipated to be required during the study. viii) History of pleomorphic lobular carcinoma in situ (LCIS), except for participants surgically managed >5 years prior to diagnosis of the current BC. ix) Evidence of ER-BC, regardless of PgRstatus. x) Undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment.
- Participants with ≥ Grade 1 peripheral neuropathy.
- Participants with an active, known, or suspected autoimmune disease.
- Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14days of randomization.
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Prior malignancy active within the previous 3 years,except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- Participants with serious or uncontrolled medical disorders.
- Other nonmalignant systemic disease that would preclude the participant from receiving study treatment or would prevent required follow-up.
- Any psychological, familial, sociological,or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule.
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Any treatment, local or systemic, including prior chemotherapy, ET, targeted therapy, and/orradiation therapy for the currently diagnosed BC prior to enrollment.
- Concurrent use (defined as within 4 weeks prior to baseline tissue sample being taken) of hormone replacement therapy or any other estrogen-containing medication, including vaginal estrogens.
- Surgical axillary staging procedure prior to enrollment (with the exception of fine-needle aspiration or core biopsy).
- Surgical excisional biopsy of primary tumor.
- Participants for whom upfront ET alone is judged clinically appropriate as optimal neoadjuvant therapy.
- Treatment with botanical preparations (eg, herbal supplements, traditional Chinese medicines) intended for general health support or to treat the disease under study within 2weeks prior to randomization/treatment.
- Participants who have received a live/attenuated vaccine within 30 days before the first treatment.
- White blood cells< 2,000/μL; Neutrophils < 1500/μL; Platelets < 100x 10^3/μL; Hemoglobin < 9.0 g/dL; Serum creatinine > 1.5 x ULN, unless creatinine clearance ≥40mL/min (measured or calculated using the Cockroft-Gault formula); Aspartate aminotransferase (AST)/ALT: > 3.0 x ULN; Total bilirubin > 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN).
- Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus.
- Has significant cardiovascular disease.
- Evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of myocarditis.
- History of allergy or severe hypersensitivity to any of the components or excipients used in the study treatments.