KEYNOTE-C14: This phase II study is evaluating how safe and effective a targeted therapy (olinvacimab) in combination with immunotherapy (pembrolizumab) is in people with metastatic triple-negative breast cancerA Phase II, Open-Label, Multicenter Study of Olinvacimab in Combination With Pembrolizumab in Patients With Metastatic Triple-Negative Breast Cancer

Exclusion

1. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

   - Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

2. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
3. Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 4 weeks or five half-lives (which is shorter) prior to the baseline visit
4. Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
5. Not recovered below National Cancer Institute (NCI) CTCAE (v5.0) Grade 1 or baseline from AEs due to previous therapy (patient with ≤ Grade 2 neuropathy or alopecia may be eligible)
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
7. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
8. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] controlled by curative therapy are not excluded).
9. Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
10. Has an active infection requiring systemic antibiotics
11. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
12. Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.) or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. Treated depression with ongoing antidepressant medication is not an exclusion criterion

13. Female who is pregnant* or lactating and of childbearing potential who does not agree to a reliable and adequate method of contraceptiona.

    A women of childbearing potential (WOCBP) must agree to use contraception during the treatment period and for at least 6 months (for females) after the last dose of study treatment.

    aAdequate contraception allowed in this trial is as follows

    • Hormonal contraceptives such as combined oral contraceptive pill
    • Intrauterine devices (IUD) or the implantation of intrauterine system
    • Blockage methods (spermicides and condoms/spermicides and [vaginal] diaphragm for contraception, vaginal sponges or cervical cap)
    • Sterilization surgery such as tubal ligation in females *A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
14. Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg) or seizure
15. Class III or IV heart failure by New York Heart Association (NYHA) classification
16. Requiring therapeutic anticoagulation treatment (prophylactic therapy with low-molecular weight heparin is allowed)
17. Serious Grade 4 venous thromboembolic event including pulmonary embolism
18. Moderate to severe proteinuria as demonstrated by urine dipstick for proteinuria ≥2+. For patients with ≥2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible.
19. History of abdominal fistula or gastrointestinal perforation, or serious GI bleeding within 6 months
20. History of severe arterial thromboembolic event within 12 months of start of study drug
21. Major surgery within 4 weeks prior to initiation of study treatment. (If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention).
22. A known history of severe hypersensitivity (≥Grade 3) to study drugs and/or any of its excipients.
23. Has had an allogenic tissue/solid organ transplant.
24. Unable to participate in the trial according to the investigator's decision.
25. Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted
26. Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment