Phase II Trial of Ivonescimab in Combination With Carboplatin + Docetaxel in Patients With Early Stage Triple Negative Breast Cancer
This is a single arm phase II trial combination of ivonescimab and carbo-docetaxel every 3 weeks for 6 cycles in patients with early-stage triple negative breast cancer. The trial is designed to test the safety and efficacy of adding ivonescimab in patients with early TNBC undergoing neoadjuvant chemotherapy with carboplatin and docetaxel. Patients will receive ivonescimab 20 mg/kg IV on Day 1 of each cycle, and carboplatin AUC6 and docetaxel 75 mg/m2 on Day 1 of each cycle for 6 cycles. Cycles will be 21 days for a total of 6 cycles. Curative intent surgery will be performed within 6 weeks (maximum 12 weeks) time frame upon completion of last dose of chemoimmunotherapy. The surgical pathology information will be used for assessment of pathological response, which serve as the primary endpoint of this study. Patients will undergo assessment at baseline, C1D1 of each cycle and end of treatment visit for collection of treatment-emergent adverse events, evaluated by CTCAE v5.0. Patient reported outcomes will be collected at cycles 1, 4, and 6, and at EOT. All study patients will be followed for at least 5 years for EFS and OS follow up. Research biopsies, peripheral blood and stool samples will be collected at the following time points: baseline, C4D1 (+/-14 days), and surgery (+/-14 days). Baseline and EOT breast MRI will be performed as standard of care for assessment of clinical response. Mid treatment breast ultrasound (C4D1 +/-14 days) will be repeated as standard of care to assess clinical response to treatment. Mid-treatment C4D1 tumor biopsy may be omitted if the primary tumor is no longer visible or the tumor deemed too small for biopsy by radiologist.
• Age ≥ 18 years of age
• ECOG ≤ 1
• High-risk early stage triple negative breast cancer (TNBC), defined by ER≤10%, PR≤10% and HER2 negative (by IHC or FISH), per ASCO/CAP guidelines
• Clinically ≥T1cN0, or any T, N1-2
• Plan to receive neoadjuvant chemotherapy and immune checkpoint inhibitor before surgery as standard-of-care treatment
• Adequate organ function as defined in the following. Specimens must be collected within 14 days prior to the start of study treatment.
‣ ANC ≥ 1,500/mm3
⁃ Platelets ≥ 100,000/mm3
⁃ Hemoglobin ≥ 9.0 g/dL.
⁃ Total serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 x ULN
⁃ AST \< 3 x ULN
⁃ ALT \< 3 x ULN
⁃ Creatinine clearance ≥ 30 mL/min
⁃ INR or PT, aPTT \< 1.5 x ULN
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test within 14 days of start of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: If egg harvesting was completed prior to enrollment, the pregnancy test may be falsely positive and the PI will assess and determine eligibility for these cases.
• Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix B), not breastfeeding, and at least one of the following conditions applies:
• \-- Not a woman of childbearing potential (WOCBP) as defined in Appendix B OR Females of child-bearing potential must be willing to use effective contraception during study and for 120 days after the last dose.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix B of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.