Title
A Phase 2, Randomized, Multicenter, Open-Label Neoadjuvant Study Evaluating Zanidatamab in Combination With Chemotherapy in Participants With HER2-Positive Breast Cancer

Description
A Phase 2, Randomized, Multicenter, Open-label Neoadjuvant Study Evaluating Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer

Objective
Primary:
1. To determine the pCR rate (ypT0/Tis ypN0) in each treatment arm (Arm A: zanidatamab + paclitaxel, Arm B: zanidatamab + docetaxel + carboplatin, Arm C: trastuzumab + pertuzumab +docetaxel + carboplatin)

Secondary:
1. To assess the distribution of RCB classification and scores at time of surgery in each treatment arm.
2. To assess the safety and tolerability of zanidatamab in combination with chemotherapy and as monotherapy following surgery.
3. To evaluate the rate of conversion to BCS in each treatment arm.
4. To evaluate EFS in each treatment arm.
5. To evaluate OS in each treatment arm.
6. To evaluate participant-reported tolerability of zanidatamab in combination with chemotherapy in participants with HER2-positive breast cancer.
7. To evaluate the PK of zanidatamab.
8. To evaluate the immunogenicity of zanidatamab.

Treatment The purpose of this study is to see if zanidatamab is safe and effective, when combined with chemotherapy, in treating people who has Human Epidermal Growth Factor Receptor 2 (HER2)-positive, early-stage breast cancer

Key Eligibility Inclusion Criteria:

Has Stage II or III histologically confirmed invasive breast carcinoma.

Has histologically confirmed HER2-positive breast cancer

Has a known hormone receptor (HR) status of the primary tumor

Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive.

Agrees to undergo a mastectomy or breast conserving surgery (BCS) after neoadjuvant therapy.

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Adequate organ function

Has an LVEF >/= 50% as determined by either ECHO or MUGA obtained within 4 weeks prior to first dose of study intervention.
Adequate contraceptive precautions


Applicable Disease Sites
Breast

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital