NiVOlumab for Luminal advanced/metastatic breast cancer to Taper ct-dnA In endocrine REsistance
Conditions
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male/female participants who are at least 18 years of age. 2.Men/Women with advanced BC not amenable to curative therapy. 3.Patients with luminal BC defined by histologically documented HR+ and HER2- tumors by local testing: a)HER2 negativity is defined as either of the following by local laboratory assessment: IHC 0, IHC 1+ or IHC2+/in situ hybridization (ISH) negative as per most recent American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline (ISH negative is defined as a ratio of HER2 to CEP17 1% of cells expressing HR via IHC analysis as per most recent ASCO-CAP guideline. 4.The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 5.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6.Postmenopausal, as defined by the study protocol. 7.Pre/perimenopausal. 8.Patients who have not received or have received one ET line for advanced BC. 9.Prior radiation therapy for metastatic disease is permitted. Patients must have recovered from radiotherapy toxicities prior to allocation. 10.Availability of formalin-fixed paraffin-embedded (FFPE) tumour block for biomarker analysis. See Section 10.1.1 (Tumor Tissue Samples). 11.Participants must have the ability to swallow oral medication. 12. easurable disease or non-measurable (but evaluable), as defined by RECIST v1.1. 13.Adequate hematologic and end-organ function, defined by the following laboratory results (Table 5 of the protocol) obtained within 3 days prior to Cycle 1, Day 1. 14.Have corrected QT interval of = 470 milliseconds on screening ECG. Male participants: 15.A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 5 months after the last dose of nivolumab and refrain from donating sperm during this period. Female participants: 16.A female participant is eligible to participate if she is not pregnant, not breastfeeding (see Appendix 3 of the protocol). 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the allocation (see Appendix 3). 2.Has received prior therapy with an anti-PD1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. 3.Prior therapy with any CDK4/6 inhibitors as therapy for advanced BC. Note: Prior therapy with CDK4/6 inhibitors as (neo)adjuvant treatment is allowed whenever the patient has progress > 12 months since last dose of CDK4/6 inhibitor. 4. Patients who received more than two chemotherapy line for advanced BC. 5. No resolution of all acute toxic effects of prior anti-cancer therapy or major surgical procedures to NCI CTCAE version 5.0 Grade = 1 6. Uncontrolled pleural effusion, pericardial effusion, or ascites 7.Uncontrolled hypercalcemia (>1.5 mmol/L [>6 mg/dL] ionized calcium or serum calcium [uncorrected for albumin] >3 mmol/L [>12 mg/dL] or corrected serum calcium >ULN) or clinically significant (symptomatic) hypercalcemia. 8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 9.Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable. 10. Has a history of or active or known autoimmune disease, or other syndrome that requires systemic steroids (> 10 mg daily prednisone equivalent) or autoimmune agents for the past 2 years (see exceptions at the protocol). 11.Has a prior allogeneic stem cell or solid organ transplantation. 12.Has a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia, long or short QT syndrome, Brugada syndrome, or known history of corrected QT prolongation, Torsade de Pointes, or sudden cardiac arrest. 13.Other nonmalignant systemic disease that would preclude the participant from receiving study treatment or would prevent required follow up. 14.Class III or Class IV myocardial disease as described by the New York Heart Association; a recent history (within 6 months prior to enrolment) of myocardial infarction, or symptomatic arrhythmia at the time of allocation/treatment. Has a history of allergy or hypersensitivity (=Grade 3) to study drug components. 15.Has received a live/attenuated vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG) and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Note: It is not recommended the use of live or attenuated COVID-19 vaccines within 30 days of initiation or during study treatment. However, if vaccination with these vaccines is required, please ask for advice on how to proceed the Medical Monitor. 16.Has a known history of Human Immunodeficiency Virus (HIV). 17.Active hepatitis B or hepatitis C with abnormal liver function tests 18.Has a known history of active TB (Bacillus Tuberculosis). 19.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine dynamic changes in ctDNA after 4 weeks of nivolumab in combination with palbociclib and letrozole, anastrozole or fulvestrant;Secondary Objective: 1. To determine the efficacy of nivolumab, palbociclib and letrozole, anastrozole or fulvestrant treatment in non-responder patients. 2. Correlative analysis of biomarkers (from mandatory tumor and blood samples collected during the study) and efficacy of treatment. 3. To identify changes in the distribution of somatic mutations within the different populations and timepoints. 4. To assess the safety and tolerability of nivolumab, palbociclib and letrozole, anastrozole or fulvestrant treatment in non-responder patients;Primary end point(s): mVAFR defined as the median of the logarithm of all VAF ratios (VAFpost/VAFpre) for all mutations at each time point. mVAFR = m(log (VAFpost / VAFpre)) VAFpost will be measured at C4D1 VAFpre will be measured at C3D1;Timepoint(s) of evaluation of this end point: From baseline until cycle 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.1. Clinical Benefit Rate (CBR) defined as the proportion of patients with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) or Non-PR/Non-progression disease (PD) lasting = 24 weeks, based on local investigator´s assessment according to RECIST v1.1. 1.2. Progression free survival (PFS) defined as the time from allocation to the first occurrence of disease progression, as determined locally by the investigator using RECIST v.1.1, or death from any cause, whichever occurs first. 1.3. Duration of response (DoR) defined as the time from the first occurrence of a documented objective response to disease progression, as determined locally by the investigator through use of RECIST v.1.1, or death from any cause, whichever occurs first. 1.4. Time to response (TtR) defined as the time from allocation to the first objective tumor response (tumor shrinkage of =30%) observed for patients who achieved a CR or PR. 1.5. Overall survival (OS) defined as the time from allocation to death from any cause (OS will be determined at the end of the study). 1.6. Overall Response rate (ORR) defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria 1.7. PFS on study treatment compared to PFS on prior line of therapy (pre-PFS) in patients who receive a prior line of therapy in the metastatic setting. 1.8. To determine the ORR, PFS,based on iRECIST. 1.1. To correlate early ctDNA dynamics (mVAFR) with PFS and ORR in non-responder patients. 1.2. To correlate PAM50 intrinsic subtype with clinical benefit and early dynamic changes in ctDNA (mVAFR) in responder and non-responder patients 1.3. To correlate PD1 mRNA expression with early dynamic changes in ctDNA (mVAFR) in responder and non-responder patients and PFS and ORR in non-respon | — |
Countries
Spain
Contacts
Public ContactAREA DE INVESTIGACION CLINICA
SOLTI
Outcome results
None listed