Neoadjuvant Angiogenesis-Targeting Bispecific Chemoimmunotherapy for TNBC

NCT07743632 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IIT-2026-NeoASPECT
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will test the effectiveness of two standard neoadjuvant chemotherapy regimens plus an investigational drug (ivonescimab) that has dual action as both immunotherapy and therapy targeting the tumor's blood supply. This investigational drug is called ivonescimab.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Keywords

Tumor-infiltrating lymphocytes; Neoadjuvant chemotherapy; Neoadjuvant immunotherapy; Angiogenesis; VEGF

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate in the breast and axilla in the two treatment arms.

  Determine the rates of pathologic complete response (pCR) with ivonescimab-containing neoadjuvant systemic therapy among patients with low and high stromal tumor-infiltrating lymphocytes (sTILs), as evidenced by absence of invasive disease in breast and axillary lymph nodes (ypT0/Tis ypN0) determined by histopathological examination.

  At time of definitive breast surgery

Secondary Outcomes (3)

• Treatment-related adverse events

  Start of study treatment (cycle 1 day 1) until 30 days after last dose of study treatment (90 days for serious and immune-related adverse events)

• Event-free survival (EFS)

  Up to 5 years after enrollment

• Overall survival (OS)

  Up to 5 years after enrollment

Study Arms (2)

Low-sTILs cohort (sTILs <30%)

OTHER

4 cycles of carboplatin AUC 6 plus docetaxel 75mg/m2 plus ivonescimab 20mg/kg every 21 days, followed by 4 cycles of doxorubicin + cyclophosphamide + ivonescimab 20mg/kg every 21 days.

Drug: Carboplatin; Drug: Docetaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Ivonescimab

High-sTILs cohort (sTILs ≥30%)

OTHER

4 cycles of carboplatin AUC 6 plus docetaxel 75mg/m2 plus ivonescimab 20mg/kg every 21 days. Patients with lack of complete imaging response (by MRI) after 4 cycles will receive two additional cycles of carboplatin AUC 6 plus docetaxel 75mg/m2 plus ivonescimab 20mg/kg every 21 days.

Drug: Carboplatin; Drug: Docetaxel; Drug: Ivonescimab

Interventions

Carboplatin DRUG

Commercially available

Also known as: Paraplatin

High-sTILs cohort (sTILs ≥30%); Low-sTILs cohort (sTILs <30%)

Docetaxel DRUG

Commercially available

Also known as: Taxotere

High-sTILs cohort (sTILs ≥30%); Low-sTILs cohort (sTILs <30%)

Doxorubicin DRUG

Commercially available.

Also known as: Adriamycin

Low-sTILs cohort (sTILs <30%)

Cyclophosphamide DRUG

Commercially available.

Also known as: Cytoxan

Low-sTILs cohort (sTILs <30%)

Ivonescimab DRUG

Ivonescimab is a bispecific antibody targeting PD-1 and VEGF. Ivonescimab will be supplied for participants by Summit Therapeutics.

Also known as: SMT112, AK112

High-sTILs cohort (sTILs ≥30%); Low-sTILs cohort (sTILs <30%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• years of age or older
• Histologically confirmed cT1c-T3 N0 or cT1-T3 N1-N2 triple-negative breast cancer
• The invasive tumor must be hormone receptor poor, defined as both estrogen receptor (ER) and progesterone receptor staining in ≤ 10% of invasive cancer cells by IHC.
• The invasive tumor must be HER2-negative based on the current ASCO-CAP guidelines 79.
• Subjects with bilateral synchronous triple-negative breast cancer are eligible if they meet other eligibility criteria.
• No previous ipsilateral breast surgery for the current breast cancer
• No previous chemotherapy, immunotherapy, targeted therapy, endocrine therapy, or radiotherapy for the current breast cancer
• ECOG Performance Status 0 or 1, documented within 21 days prior to the start of study treatment (Appendix A)
• Breast and axillary imaging (including MRI and either mammogram and/or ultrasound, per standard of care) within 56 days (8 weeks) prior to treatment initiation
• Subjects with clinically and/or radiographically abnormal axillary or internal mammary lymph nodes should have pathologic assessment of disease status with image-guided biopsy or fine needle aspiration unless deemed medically unsafe
• Co-enrollment in the PROGECT (HSC #12614) observational registry protocol
• Archival breast tumor tissue has been obtained or has been requested for use, which should include either a formalin-fixed paraffin-embedded (FFPE) block, or sixteen slides (fourteen 5-micron uncharged unstained slides plus either two H\&E slides or two 5-micron charged unstained slides) - from primary breast tumor only.
• Neuropathy: No baseline grade 2 or above neuropathy
• Not pregnant, not breastfeeding, and at least one of the following applies:

You may not qualify if:

• Current or anticipated use of other investigational agents while participating in this study
• Clinically or radiographically detected metastatic disease
• Inflammatory breast cancer
• Prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen.
• \- Note: Patients with squamous cell or basal cell carcinoma of the skin, ductal carcinoma in situ (DCIS) of the breast, or carcinoma in situ (CIS) of the uterine cervix who have undergone definitive therapy are not excluded from participation
• History of allergic reactions attributed to carboplatin, docetaxel, doxorubicin, or cyclophosphamide
• History of severe (≥ grade 3) hypersensitivity to ivonescimab or any of its excipients, or to any other monoclonal antibody
• Prior treatment with a VEGF inhibitor or with an anti-PD-1, anti-PD-L1, anti-PD-L2 inhibitor or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40, CD137)
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to starting study treatment, including but not limited to:
• 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)
• Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to starting study treatment. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to institutional guidelines.
• Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
• Major surgical procedures or serious trauma within 4 weeks prior to start of study treatment, major surgical procedures planned for within 4 weeks after the first dose of study treatment, or minor local procedures within 3 days prior to start of study treatment (as determined by the investigator).
• \- Note: Central venous catheterization and port implantation within 3 days prior to start of study treatment are allowed.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Carboplatin; Docetaxel; Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Priyanka Sharma, MD

  The University of Kansas Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KUCC Navigation

CONTACT

913-588-3671; kucc_navigation@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 4, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2033
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share