MC# 17-25 - A Phase I, first-in-man, multicenter, open-label, dose-escalation study of single-agent GBR 1302 in subjects with HER2 positive cancers
Agent(s): GBR 1302
Disease Type(s): Breast, Gastric
Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
Molecular Target(s): ERBB2 (HER2)
Mechanism of Action
GBR 1302 is a humanized, bispecific antibody having anti-HER2 specificity. GBR 1302 was designed to simultaneously engage T lymphocytes and the HER2 antigen on tumor cells, and thus bridge cytotoxic T lymphocytes to tumor cells, thereby killing the bound target cells.
In this study, the sponsor and investigators want to learn:
- How much GBR 1302 can be given with an acceptable level of side effects
- The effects of GBR 1302
- How much GBR 1302 is absorbed into the blood and how fast it is removed
- How proteins that indicate the status of disease are affected with use of GBR 1302
- If the body develops proteins that work against GBR 1302
- Signed written informed consent that is consistent with ICH-GCP guidelines and local legislation.
- Criteria for tumor pathology are as follows:
- For Part 1a: Progressive HER2-positive solid tumor which has been treated with all therapy (including HER2 therapy, for those patients with ASCO/CAP defined HER2+ tumors) known to confer clinical benefit.
- For Part 1b: Her2 2+/3+ breast cancer which has been treated with all therapy (including HER2 therapy, for those patients with ASCO/CAP defined HER2+ tumors) known to confer clinical benefit.
- Evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Aged 18 years or older.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
- Recovered from any previous surgery and no history of major surgery within the last 28 days prior to start of study medication in the opinion of the Investigator.
- Absolute neutrophil count ≥ 1500/μL.
- Platelets ≥75000/μL.
- Total bilirubin ≤ 1.5x institution ULN; (< 3xULN is acceptable for subjects with benign conditions like Gilbert’s Syndrome).
- AST and ALT ≤ 3.0x institution ULN (in case of known liver metastases: AST and ALT ≤ 5x ULN).
- Creatinine ≤1.5 x institution ULN.
- Each woman of childbearing potential must have a negative serum pregnancy test result within 7 days prior to first dosing and a negative urine pregnancy test predose on Day 1. She must be willing to use a highly effective form of contraception for the duration of the study and for at least 3 months after the last dose of study medication. Methods like periodic abstinence, post ovulation procedures and withdrawal are not considered adequate. Each woman will be considered to have childbearing potential unless she has been surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy or has been post-menopausal for at least two years. For postmenopausal women only, FSH testing will be performed at screening to confirm non-childbearing potential (FSH ≥ 40 IU/L).
- Men with partners of childbearing potential must be willing to use condoms in combination with a second effective method of contraception during the study and for at least 3 months after the last dose of study medication. Each man will be considered as potent unless surgically sterilized (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
- Subjects who will enter Cohort 1 or 2 need a pre-existing, functioning, central venous access in place for the administration of the study drug.
- Active infectious disease considered by the Investigator to be incompatible with the protocol.
- Serious illness or concomitant non-oncological disease considered by the Investigator to be incompatible with the protocol.
- Has not recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, molecular-targeted, or radiotherapies to at least CTCAE ≤ Grade 1 except in case of liver metastases or Gilbert’s Syndrome or alopecia.
- Brain metastases that are symptomatic or untreated or that require current therapy.
- Previous antineoplastic treatment with immune checkpoint regulator or comparable immunotherapy within 8 weeks of starting study medication, chemotherapy, radiotherapy, molecular-targeted therapy, or biological therapies (including HER2-directed therapies) within 4 weeks of starting study medication, or hormone therapy within 2 weeks of starting study medication.
- Use of any investigational drug within the past 4 weeks before start of study medication or concomitantly with this study except for investigational immune-stimulatory therapy (e.g. checkpoint-regulator targeted treatment). The minimum washout period should be 8 weeks before starting the study medication.
- Any history or evidence of clinically significant cardiovascular disease defined as at least one of following criteria:
- Baseline Left Ventricular Ejection Fraction (LVEF) < 50% or major wall dyskinesias via echocardiography (ECHO).
- History or evidence of poorly controlled arterial hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure >100 mmHg).
- Cardiac arrhythmias requiring anti-arrhythmic therapy, except for beta blockers, calcium antagonists and digoxin.
- Clinically significant valvular heart disease.
- Myocardial infarction or instable angina pectoris within the previous 6 months.
- Documented history of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria.
- History of exposure to the cumulative doses of anthracyclines as follows: prior anthracycline cumulative exposure > 360 mg/m2 of doxorubicin or its equivalent.
- Severe dyspnea, pulmonary dysfunction, or need for continuous supportive oxygen inhalation.
- Unable to comply with the protocol.
- For Part 1: Active alcohol abuse, or active drug abuse, or any social behaviors and conditions not likely to be compatible with adherence to the study requirements (at the discretion of the Investigator).
- For Part 2: Subject was previously treated in the study.
- Pregnant or breast feeding.
- Diagnosed with another malignancy that requires active therapy.
- Known allergy to any of the ingredients in the formulation or known allergy to any related class of compounds.
- Employee of the clinical study site or any other individual involved with the conduct of the study, or immediate family members of such individuals
- Any other reason that, in the investigator’s opinion, prohibits the inclusion of the subject into the study.
- Dallas, TX - Mary Crowley Cancer Research - Medical City