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Label indication Herceptin is a HER2/neu receptor antagonist indicated in adults for: The treatment of HER2-overexpressing breast cancer. ( 1.1 , 1.2 ) The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. ( 1.3 ) Select patients for therapy based on an FDA-authorized companion diagnostic for Herceptin ( 1 , 2.2 ). FDA label
Also known as Herceptin®
Trastuzumab · 6 trials · 8 indications
Evaluate the ability of tucatinib in combination with trastuzumab/pertuzumab or TDM-1 to prolong intracranial progression free survival (PFS) in patients compared to historical controls. PFS is defined as the time from the day of study treatment initiation until evidence of intracranial disease progression per RANO-BM or death from any cause.
Pathological complete response (pCR) is defined as absence of invasive tumour cells in the breast and in the axillary lymph nodes at the time of surgery (ypT0/ypTis ypN0) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual. The presence of in situ cancer after trial treatment in the absence of residual invasive disease constitutes a pCR.
Progression Free Survival is defined from the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST 1.1 or death from any cause, whichever occurs first.
cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (\<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
| Arm | Type | Description |
|---|---|---|
| Experimental Group | EXPERIMENTAL | Trastuzumab/pertuzumab + tucatinib or T-DM1 + tucatinib 300mg of tucatinib taken orally twice a day. Taken on Days 1-21 of a 21 Day cycle (3 Weeks). Trastuzumab/Biosimilar administered per current package insert based on site standard of care guidelines Pertuzumab or Biosimilar administered per current package insert based on site standard of care guidelines Trastuzumab Emtansine (T-DM1) administered per current package insert based on site standard of care guidelines |
| Paclitaxel plus trastuzumab and pertuzumab | ACTIVE_COMPARATOR | Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. |
| Palbociclib plus letrozole plus trastuzumab and pertuzumab | EXPERIMENTAL | Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. |
| NH: Trastuzumab + Vinorelbine | EXPERIMENTAL | * Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle |
| NHA: Trastuzumab + Vinorelbine + Avelumab | EXPERIMENTAL | * Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab |
| NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab | EXPERIMENTAL | * Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab * Utomilumab is administered intravenously once per cycle |
| Cohort A: Tucatinib + Trastuzumab | EXPERIMENTAL | Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
| Cohort B: Tucatinib + Trastuzumab | EXPERIMENTAL | Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
| Cohort C: Tucatinib Monotherapy | EXPERIMENTAL | Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. |
| Cohort 1 | EXPERIMENTAL | 0.04 mg/kg CpG 7909 |
| Cohort 2 | EXPERIMENTAL | 0.08 mg/kg CpG 7909 |
| Cohort 3 | EXPERIMENTAL | 0.12 mg/kg CpG 7909 Injection once weekly |
| Cohort 4 | EXPERIMENTAL | 0.16 mg/kg CpG 7909 |
| 1 | EXPERIMENTAL | Combination of SU011248 (37.5 mg once daily \[Schedule 2/1\]) with docetaxel (75 mg/m2 every 3 weeks) and trastuzumab (therapeutic dose) |
| Name | Type | Description |
|---|---|---|
| Trastuzumab | DRUG | Administer per current package insert based on site standard of care guidelines |
| Trastuzumab Emtansine (T-DM1) | DRUG | Administer per current package insert based on site standard of care guidelines |
| Pertuzumab | DRUG | Administer per current package insert based on site standard of care guidelines |
| Tucatinib | DRUG | 300 mg orally twice daily (21 Day Cycle) |
| Paclitaxel | DRUG | Chemotherapy plus HER2 Blockade |
| Palbociclib | DRUG | CDK Inhibition plus Hormonal Therapy plus HER2 Blockade |
| Letrozole | DRUG | CDK Inhibition plus Hormonal Therapy plus HER2 Blockade |
| Vinorelbine | DRUG | work by interfering with cell division, which leaves the tumor unable to grow and spread |
| Avelumab | DRUG | monoclonal antibody directed against the human immunosuppressive ligand programmed death-ligand 1 (PD-L1) protein |
| Utomilumab | DRUG | Utomilumab is an antibody designed to stimulate the body's immune system to fight cancer cells |
| 0.04 mg/kg CpG 7909 | DRUG | 0.04 mg/kg CpG 7909 by subcutaneous Injection once weekly until progression or 24 weeks |
| Herceptin® | DRUG | Herceptin® (maintenance dose per the manufacturer's directions) followed by a subcutaneous injection of CpG 7909. |
| 0.08 mg/kg CpG 7909 | DRUG | 0.08 mg/kg CpG 7909 by subcutaneous Injection once weekly until progression or 24 weeks |
| 0.12 mg/kg CpG 7909 | DRUG | 0.12 mg/kg CpG 7909 by subcutaneous Injection once weekly until progression or 24 weeks |
| 0.16 mg/kg CpG 7909 | DRUG | 0.16 mg/kg CpG 7909 by subcutaneous Injection once weekly until progression or 24 weeks |
| Herceptin | DRUG | Trastuzumab will be administered intravenously on Day 1 before docetaxel - loading dose of 4 mg/kg over 90-minute on Day 1 followed by weekly maintenance doses of 2 mg/kg on Days 1, 8, 15 given as 30-minute infusions if the initial loading dose was well tolerated. Loading dose of 8 mg/kg over 90-minute on Day 1 followed by 3-weekly maintenance doses of 6 mg/kg given as 90-minute infusions. The administration of 6 mg/kg will be repeated on Day 1 every 3 weeks. |
| Sunitinib | DRUG | SU011248 will be administered at 37.5 mg once daily for 2 weeks every 3 weeks (Schedule 2/1) starting from Day 2, when in combination with docetaxel. SU011248 will be administered at the starting dose of 37.5 mg daily in a continuous regimen when docetaxel is discontinued. |
| Taxotere | DRUG | The starting dose of docetaxel will be 75 mg/m2 every 3 weeks, administered on Day 1 of each cycle as a 1-hour IV infusion. |
Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed cons...
Trastuzumab is a monoclonal antibody developed by Pfizer (ticker PFE) for HER2-positive cancers. It is being studied in breast cancer, brain metastases, and metastatic colorectal adenocarcinoma. Trastuzumab is also known by the brand name Herceptin and is sometimes used in combination with pertuzumab, referred to as trastuzumab plus pertuzumab.
Trastuzumab targets ERBB2, also known as HER2, and acts as an inhibitor of this receptor. By binding ERBB2, the antibody is directed at HER2-positive tumors, which is why the clinical programs select patients by HER2 biomarker status across breast cancer and other solid tumors.
Trastuzumab is developed by Pfizer, Inc., which trades under the ticker PFE. The brand name Herceptin is associated with trastuzumab, and the asset also appears as a combination product pairing trastuzumab with pertuzumab.
Trastuzumab is in Phase 2 clinical development across its listed cancer indications, including breast cancer, brain metastases, and metastatic colorectal adenocarcinoma. It is an investigational asset in these programs rather than a newly approved product, and the trials recorded span Phase 2 studies in the United States and Europe.
Trastuzumab trials include NCT05323955, a Phase 2 study adding tucatinib to prevent secondary brain metastases after intracranial progression on trastuzumab/pertuzumab or T-DM1 in HER2+ breast cancer, and NCT03644186, a completed Phase 2 trial in postmenopausal ER-positive, HER2-positive breast cancer. Other studies include NCT03414658 in advanced HER2+ breast cancer and NCT03043313 with tucatinib in HER2+ colorectal cancer.