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A basket trial of DS-8201a, a novel HER2-targeted antibody-drug conjugate, for HER2 amplified solid tumors identified by ctDNA analysis (HERALD trial)

HERALD Study

Taniguchi Hiroya

Aichi Cancer Center Hospital

1-1 Kanokoden, Chikusa-ku, Nagoya-shi Aichi, Japan

HERALD_core@east.ncc.go.jp

clinical trial coordinating committee

National Cancer Center Hospital East

6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan

+81-4-7133-1111

HERALD_core@east.ncc.go.jp

recruiting

Oct. 07, 2019

Interventional

This study is an open-label, single arm, multicenter phase II basket-type study to evaluate the efficacy and safety of DS-8201a in patients with solid malignancies with HER2 amplified in circulating tumor DNA who are refractory to or intolerant to standard chemotherapy.

treatment purpose

2

1. Informed consent for participation in the study is obtained at the discretion of the patient.
2. The patient is 20 years of age or older on the date of informed consent.
3. Histologically or cytologically confirmed an unresectable advanced or recurrent solid malignancy who are refractory or intolerant to stanard therapy.
4. HER2 genomic amplified is detected by analysis of blood sample using Guardant360:
5. The disease is measurable based on the Response Evaluation Criteria in Solid Tumours (RECIST) guidelines version 1.1.
6.Adequate organ function
7.Males and women of childbearing potential who are negative in a urine pregnancy test agree to use contraception from obtaining informed consent through 4.5months after the final administration of DS-8201a.

[Principal Analysis Cohort (Enrollment Completed)]
1. Has a history of prior treatment with antibody-drug conjugate (ADC) consists of DS-8201a or an exatecan derivative.
2.Patients with stomach cancer, breast cancer, colorectal cancer, lung cancer, biliary tract cancer, uterine cancer sarcoma and osteosarcoma, who high expression of HER2 has been confirmed by evaluation by tumor tissue assessment.
3.Has spinal cord compression or clinically active central nervous system metastases.
4.Patients with uncontrolled acute systemic infection or diabetes mellitus.
5.Medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment.
6.Have a history of other malignancies within 3 years prior to enrollment.
7.Has HIV infection. Patients who are HBs antigen positive or HBs antibody or HBc antibody positive and HBV-DNA positive. Or have active hepatitis C.
8.Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
9.having a clinically relevant corneal disease.
[Expansion cohort]
1. Has a history of prior treatment with antibody-drug conjugate (ADC) consists of DS-8201a or an exatecan derivative.
2. breast cancer patients with confirmed HER2 positive or low HER2 expression as assessed by tumor histology, or gastric cancer patients with confirmed HER2 positivity.
3. with lesions that compress the spinal cord.
4.Patients with uncontrolled acute systemic infection.
5.Medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment.
6.Have a history of other malignancies within 3 years prior to enrollment.
7. HIV infection and poorly controlled. Active or poorly controlled hepatitis B or active hepatitis C.
8.Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
9.having a clinically relevant corneal disease.

Both

solid malignancies

investigational material(s)
Generic name etc : DS-8201a
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : DS-8201a (5.4mg/kg) is administrated i.v. on day1, repeated every 21 days.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
objective response rate(ORR) assessed by investigators

safety
efficacy
Progression-free survival: PFS
Duration of response: DoR
Time to treatment failure: TTF
Disease control rate: DCR
Overall survival: OS
ORR by central assessment (Principal Analysis Cohort only)
Changes of sum of tumor diameter
AE

+81-4-7133-1111

Sept. 11, 2019