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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Drug: Ivonescimab Dose: 20 mg/kg Route: IV infusion over 60 minutes Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Drug: Carboplatin Dose: AUC6 Route: IV infusion Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Drug: Docetaxel Dose: 75 mg/m\^2 Route: IV infusion over 60 minutes Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Cedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGCedars-Sinai Medical Center Beverly Hills
Los Angeles, California, United States
RECRUITINGHuntington Cancer Center, an Affiliate of CS Cancer
Pasadena, California, United States
NOT_YET_RECRUITINGHunt Cancer Institute, an Affiliate of CS Cancer
Torrance, California, United States
RECRUITINGPathological complete response (pCR) rate
Pathological complete response (pCR) will be defined as the absence of invasive disease in the breast and lymph nodes at the time of SOC curative-intent surgery. This will be assessed at time of surgery. Pathological responses will be evaluated using residual cancer burden (RCB) classifier defined by ASCO/CAP guideline.
Time frame: 6 months (From cycle 1 day 1 till surgery)
To determine the overall safety of ivonescimab in combination with carboplatin and docetaxel in patients with early-stage TNBC by CTCAE v5.0.
Frequency and severity of treatment-emergent adverse events, evaluated by CTCAE v5.0.
Time frame: 9 months (From Cycle 1 until 90 days post last dose of study treatment)
Event-free survival (EFS)
Event-free survival (EFS) measured from start of study treatment to the first occurrence of recurrent disease, or death due to breast cancer.
Time frame: From cycle 1 day 1 till end of follow up (up to 5 years)
Overall survival (OS)
Overall survival (OS) measured from start of study treatment to death or last contact (censored)
Time frame: From cycle 1 day 1 till end of follow up (up to 5 years)
Patient-reported outcomes (PRO)
Patient-reported outcomes (PRO) will be measured by changes in the PROMIS-29 Profile physical function subscale score measured at start of study treatment and End of Treatment. The PROMIS-29 scoring provides T-scores that indicate the level of a patient's health-related quality of life compared to a reference population. A T-score of 50 represents the average score for that population. Higher scores generally indicate more of the concept being measured, such as physical function or mental health.
Time frame: 9 months
Patient-reported outcomes (PRO)
Patient-reported outcomes (PRO) will be measured by changes in the PROMIS Fatigue 7a measured at start of study treatment and End of Treatment. The PROMIS 7a scoring system uses a standardized T-score with a mean of 50 and a standard deviation of 10, allowing for comparison of individuals to the general population. A higher T-score generally indicates a higher level of the specific trait being measured (e.g., fatigue, anxiety, depression).
Time frame: 9 months
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