BCT 1902 (Neo-N): A phase II trial evaluating the efficacy of nivolumab or nivolumab plus relatlimab with paclitaxel and carboplatin as neoadjuvant therapy in early stage triple negative breast cancers

ACTRN 12619001308189

Brief Summary

This study aims to find out how well using immunotherapya treatment that uses a person's immune system to fight cancer on its own before starting standard chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, or starting treatment with immunotherapy at the same time as standard chemotherapy, helps to reduce tumour size before surgery in patients with previously untreated early stage triple negative breast cancer.

Intervention/Treatment

• Drug: Nivolumab
• Drug: Carboplatin
• Drug: Relatlimab
• Drug: Paclitaxel

Inclusion Criteria

1. Female or male, age >= 18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
3. Previously untreated non-metastatic (M0) TNBC meeting Stage I or II criteria according to AJCC Cancer Staging Manual, 8th Edition, 2017 as assessed by the local investigator on the basis of mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue (MMG) and/or ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body   (US) of the breasts, and US or clinical examination of the axillaarmpit, underarm:
   • Stage I cT1c cN0;
     Stage IIA cT1 cN1; cT2 cN0;
     Stage IIB cT2 cN1; cT3 cN0.
   • Contralateral in situ only disease is permitted;
   • In the event of abnormal imaging of the axilla, nodal status should be confirmed by cytology.
4. Clinically node positive participants should undergo computed tomography (CT) scan or PET CT of chest/abdomen (and bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities if clinically indicated) to exclude metastases. Those participants with equivocal finding on staging should have biopsies performed to confirm or exclude metastatic disease if possible.
5. Non-metastatic, potentially operably, unilateral triple negative breast cancer, histologically defined as:
   • ER negative: with < 1% of tumour cells positive for ER by IHC irrespective of staining intensity; AND
   • PR negative: with < 10% tumour cells positive for PR by IHC irrespective of staining intensity; AND
   • HER2 negative:
     1. IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within <= 10% of the invasive tumour cells; OR
     2. IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of invasive tumour cells; OR
     3. ISH (FISH or SISH) negative based on:
        • Single-probe average HER2 copy number < 4.0 signals/cell; OR
        • Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell; OR
        • As per ASCO-CAP 2018 Guidelines.
6. Able to commence study treatment within 14 days of randomisation/registration.
7. Surgery is able to be undertaken within 4 weeks of final dose of neoadjuvant IV therapy. Pre-operative radiation is not permitted for any participant with operable cancer after final paclitaxel.
8. Adequate organ function. All screening laboratory tests should be performed within 14 days of randomisation/registration.
9. Screening laboratory values must meet the following criteria (using NCI-CTCAE V5.0):
   • WBC >= 2 x 10^9/L;
   • Neutrophilsa type of white blood cell that act as a first responder to infections in the body >= 1.5 x 10^9/L;
   • Platelets >= 100 x 10^3/µL;
   • Haemoglobin >= 9.0 g/dL;
   • Serum creatinine <= 1.5 x ULN or calculated creatinine clearance >= 50 mL/min (using the Cockcroft Gault formula);
   • AST/ALT <= 3.0 x ULN;
   • Total bilirubin <= 1.5 x ULN except participants with Gilbert Syndrome who must have a total bilirubin level <= 3.0 x ULN.
10. Left ventricular ejection fraction (LVEF) of >= 50% assessed by echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow (ECHO) or multigated acquisition (MUGA) scan performed at screening (no more than 4 weeks before study entry).
11. Negative pregnancy test or confirmation of post-menopausal status for female participants. Women who have undergone surgical sterilisation (bilateral oophorectomyremoval of one (unilateral) or both (bilateral) ovaries, bilateral salpingectomyremoval of one (unilateral) or both (bilateral) fallopian tubes/tubal ligation, or hysterectomycomplete or partial removal of the uterus) do not require pregnancy testing.
    • Negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG within 14 days of randomisation/registration and within 7 days before the first dose of study treatment. The pregnancy test will be repeated within 24 hours before the first dose if outside this window.
      OR:
    • Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
      1. Women < 50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments with no Mirena® IUD in situ and if they have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution.
      2. Women >= 50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments with no Mirena IUD in situ or endometrial ablation. If Mirena IUD or endometrial ablation and age < 60 years, LH and FSH should be in the postmenopausal range.
12. Female participants of childbearing potential must agree to follow instruction for method(s) of contraception from the time of enrolment for the duration of treatment and for at least 5 months after completing Nivolumab and/or Relatlimab treatment;
13. Be willing and able to provide written informed consent for the study. The participant may also provide consent for future unspecified biomedical research. However, the participant may participate in the main study without participating in future unspecified biomedical research.
14. The participant has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
15. The participant agrees to make tumour (diagnostic core biopsyremoval of a section of tissue to analyse for cancer cells and surgical specimen) available for submission for central pathology review and to conduct translational studies as part of this protocol.