Phase 1/2, Multicenter, Open-label, Multiple-Dose First-in-human Study of U3-1402, in Subjects with HER3 Positive Metastatic Breast Cancer
Phase I/II Study of U3-1402 in Subjects with HER3 Positive Metastatic Breast Cancer
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
completed
Dec. 13, 2016
180
Interventional
Multicenter, open-label
Dose Escalation Part: To assess safety and tolerability, To determine MTD
Dose Finding Part: To assess safety and efficacy, To assess the safety of alternative dosing schedule(s) of U3-1402, To determine a recommended doses for Expansion
Dose Expansion Part: To assess the safety and evaluate the efficacy at the recommended doses for Expansion in subject with HER2 negative breast cancers (including TNBC).
treatment purpose
1-2
Common Inclusion Criteria
1. Has a pathologically documented advanced/unresectable or metastatic breast cancer.
2. Documented HER3-positive disease measured by immunohistochemistry (IHC) .
3. Refractory to or intolerable with standard treatment, or for which no standard treatment is available.
4. Age >= 20 years in Japan, >= 18 years in the United States.
5. Has an Eastern Cooperative Oncology Group Performance Status 0-1.
6. Has left ventricular ejection fraction >= 50%.
7. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part
1. Has received >= 2 and =< 6 prior chemotherapeutic regimens for breast cancer, >= 2 of which were administered for treatment of advanced/unresectable or metastatic disease. At least 1 prior chemotherapeutic regimen must have included a taxane administered in the neoadjuvant, adjuvant, or advanced setting. (With exception of Dose Expansion Part TNBC cohort.)
Additional Inclusion Criteria for Dose Expansion Part
1. Is able to submit a fresh tumor biopsy sample prior starting study treatment. (If subjects have already submitted fresh tumor biopsy sample for HER3 expression, they don't need to submit it again.)
2. Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort.)
Additional Inclusion criteria for Dose Expansion Part TNBC cohort:
1. Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines.
2. Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.
1. Prior treatment with a HER3 antibody.
2. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201).
3. Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment.
4. Has a medical history of myocardial infarction or unstable angina.
5. Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females
6. Has any history of interstitial lung disease (pulmonary fibrosis or radiation pneumonitis) or is suspected to have such disease by imaging during screening.
7. Has clinically significant corneal disease.
Additional Exclusion criteria for Dose Expansion Part
Prior treatment with an antibody-drug conjugate (ADC) which consists of govitecan derivative (eg, IMMU-132).
20age old over
No limit
Both
Metastatic Breast Cancer
investigational material(s)
Generic name etc : U3-1402
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Intravenous
control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -
safety
efficacy
Dose Escalation Part: Safety, Tolerability
Dose Finding Part: Safety, Efficacy
Dose Expansion Part: Safety, Efficacy
Assessment of tumor response to U3-1402 using RECIST ver. 1.1
safety
efficacy
pharmacokinetics
pharmacodynamics
Dose Escalation Part: Pharmacokinetics, Efficacy, Incidence of anti-drug antibodies (ADAs) against U3-1402
Dose Finding Part: Pharmacokinetics, Incidence of ADAs against U3-1402
Dose Expansion Part: Pharmacokinetics, Incidence of ADAs against U3-1402 relationship between efficacy of U3-1402 and HER3 expression
