• Signed Informed Consent Form (ICF) for Trial Registration;

• Aged ≥18 years old;

• Histologically confirmed invasive triple negative breast cancer (TNBC). TNBC defined as ER negative, PgR negative (ER and PgR negative as defined by Allred score 0/8, 1/8 or 2/8 or stain in \<1% of cancer cells) or PgR unavailable, and HER2 negative (immunohistochemistry 0/1+ or negative in situ hybridization) as determined by local laboratory and recorded in the patients notes;

• Planned definitive surgical treatment after at least 6 cycles of neoadjuvant chemotherapy (NACT) Patients currently receiving SOC pembrolizumab, or having previously received SOC pembrolizumab but subsequently discontinued treatment, in combination with NACT are eligible for Trial Registration;

• Radiographically measurable tumour mass assessable for new distinct radio-opaque marker insertion and repeated biopsies on the NACT mid-assessment standard of care imaging modality;

• Eastern Oncology Cooperative Group (ECOG) performance status 0-1;

• Considered fit enough to have breast cancer surgery with curative intent;

• Considered fit to complete at least 2 weeks of pre-operative trial treatment in the WOP;

• Patients must be suitable for a mandatory pre-treatment baseline biopsy performed Day -1 or 1 of the window of opportunity (WOP) and a post-treatment biopsy performed on Day 14 of the WOP. Registered patients who are approached for Trial Entry will be required to consent to the pre- and post- WOP treatment biopsy. If it is deemed unsafe to proceed with biopsy upon Trial Entry the patient will not be eligible for participation in the trial.

⁃ Patients with clinical stage II or III disease or clinical suspicion of metastatic disease must have staging studies to exclude metastatic disease if this is standard of care, and staging methods should be used as per standard of care (axillary lymph nodes or internal mammary node involvement will not be regarded as evidence of metastatic disease);

⁃ Patients with previous invasive cancers (including breast cancer) are eligible if the treatment was completed \>5 years prior to Trial Registration, and there is no evidence of recurrent disease;

⁃ Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up schedule; those conditions should be discussed with the patient before Trial Registration;

⁃ Patients must be a) surgically sterile (i.e. if female have undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy; if male have undergone a bilateral orchidectomy); b) have a sterilised sole partner; or c) be post-menopausal; or d) must agree to practice total/true abstinence; or e) use a condom and one highly effective form of contraception in combination during the period of trial treatment and be willing to do so for a period of at least 6 months following the end of trial treatment. Please refer to Section 5.4 Lifestyle Guidance for the definition of total/true abstinence and a list of the permitted highly effective forms of contraception.

∙ Post-menopausal is defined by at least one of the following criteria:

• Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments

• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution for women \< 50 years of age not using hormonal contraception or hormonal replacement therapy. Please note: in absence of amenorrhea for 1 year, a single LH and/or FSH measurement is insufficient.

• Radiation-induced oophorectomy with last menses \>1 year ago

• Chemotherapy-induced menopause with \>1 year interval since last menses

• Surgical sterilisation (hysterectomy, bilateral salpingectomy or bilateral oophorectomy)

• Signed Informed Consent Form (ICF) for Trial Entry;

• Residual disease is confirmed as at least one viable disease focus ≥1cm on trial-specific imaging performed at least 1 week following day 1 of the final cycle of NACT.

• Provision of acceptable archival diagnostic tumour tissue sample prior to Trial Entry as defined in the Investigator Laboratory Manual.

• Recovery from all acute adverse events of prior NACT or pembrolizumab to baseline or NCI CTCAE Grade ≤1, except for alopecia. Patients with irreversible toxicity not reasonably expected to be exacerbated by trial treatment may be included only after consultation with the CI or Coordinating Investigator.

• Patients must have adequate haematological, renal and hepatic function as defined by:

‣ Haemoglobin (Hb) ≥ 10 g/dL (≥ 100 g/L) with no blood transfusion in the past 28 days

⁃ Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 x 109/L)

⁃ Platelet count ≥100,000/mm3 (≥ 100 x 109/L)

⁃ Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

⁃ Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional ULN

⁃ Calculated creatinine clearance ≥51 mL/min using the Cockcroft-Gault equation (please refer to Appendix 4) or based on a 24 hour urine test or another validated test as per local practice

• Women of childbearing potential must have a confirmed menstrual period and a negative urinary or serum pregnancy test prior to Trial Entry. This should be repeated as applicable to ensure a negative pregnancy test is performed on the day of planned trial treatment.

• Confirmation that all Trial Registration inclusion criteria listed in Section 5.3.1 remain satisfied.