Olinvacimab With Pembrolizumab in Patients With mTNBC

• Drug: Olinvacimab

Inclusion Criteria

1. Female patients ≥19 years old
2. Histologically proven mTNBC* irrespective of PD-L1 status.*Histological or cytological diagnosis of relapsed/metastatic TNBC. TNBC is defined by the negative expression of estrogen receptors (ER), progesterone receptors and human epidermal receptor-2 (HER2). If there is a pathology report of the metastasis, take the histopathology of the metastases as standard. Negative for ER and progesterone receptors is defined as the expression of ER and progesterone receptors in <1% of the tumor cells by immunohistochemistry (IHC). HER2-negative is defined as a score of 0 and 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative. If the HER2 test result is 0 or 1+ by IHC, FISH detection is optional, but the result must be negative.
3. Has provided archival tumor tissue sample or newly obtained core or excisional biopsyremoval of a section of tissue to analyse for cancer cells of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.- Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut
4. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
5. Has received at least one prior line of systemic therapy for metastatic or inoperable locally advancedat a late stage, far along TNBC. Patients who have failed adjuvant chemo within 12 months should be considered as fulfilling a line of systemic therapy.
6. No previous therapy with anti-VEGF, anti-VEGFR or anti-PD-1 antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses for their metastatic disease. The use of anti-VEGF, anti-VEGFR, anti-PD-1 or anti-PD-L1 antibody in neoadjuvant or adjuvant setting will be allowed if there was no progression of disease within 6 months after the completion of treatment.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Adequate hematologic, renal, and hepatic function tests performed within 7 days prior to initiation of study treatment:
   • Hematologic tests
     • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
     • Platelets ≥ 100 x 109/L
     • Haemoglobin ≥ 9.0 g/dL (This must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin, e.g. ≥ approximately 3 months)
   • Blood coagulation tests
     • Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (UNL)
     • Activated partial thromboplastin time (aPTT) ≤ 1.5 x UNL
   • Hepatic function tests
     • Total bilirubin ≤ 1.5 x UNL
     • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
   • Renal function test – Creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patients with creatinine levels >1.5 × institutional ULN
9. HIV-infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
   • Participants on ART must have a CD4+ T cell count >350 cells/mm3 at time of screening
   • Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
   • Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (day 1)
10. Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
    • Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
    • Hepatitis B screening tests are not required unless:
      • Known history of HBV infection
      • As mandated by local health authority
11. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
    • Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
    • Hepatitis C screening tests are not required unless:
      • Known history of HCV infection
      • As mandated by local health authority
12. The patient should provide written informed consent