About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Evidence of metastatic disease.
Is currently participating in or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
Trial design
Single group
Treatments tested in this trial
Ivonescimab
DrugDrug: Ivonescimab Dose: 20 mg/kg Route: IV infusion over 60 minutes Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Carboplatin
DrugDrug: Carboplatin Dose: AUC6 Route: IV infusion Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Docetaxel
DrugDrug: Docetaxel Dose: 75 mg/m\^2 Route: IV infusion over 60 minutes Frequency: Q3W Duration: 6 cycles (Each cycle is 21 days)
Treatment groups
Trial outcomes
Primary outcomes
Pathological 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.
Secondary outcomes
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.
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.
Overall survival (OS)
Overall survival (OS) measured from start of study treatment to death or last contact (censored)
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.
Sponsors and contacts
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Cedars-Sinai Medical Center
Lead sponsor
Summit Therapeutics
Collaborator