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A clinical trial of DS-8201a for HER2 positive unresectable or recurrent biliary tract cancer: NCCH1805, HERB trial (HERB Trial)

A Phase II trial of DS-8201a for HER2 positive biliary tract cancer

32

Chigusa Morizane

National Cancer Center Hospital

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

cmorizan@ncc.go.jp

Naoko Matsui

National Cancer Center Hospital

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

+81-3-3542-2511

NCCH1805_HERB_office@ml.res.ncc.go.jpjp

COMPLETED

June. 21, 2019

Interventional

Single arm phase 2 trial

open(masking not used)

No

2

1.Adenocarcinoma or adenosquamous carcinoma is histologically diagnosed.
2.HER2-expressing was confirmed by central pathological examination of designated HER2 screening trial. HER2-expressing is defined as any of the following:
1)More than or equal to 1+ by IHC
2)Positive by ISH
3.Unresectable or recurrent biliary tract cancer.
4.No moderate or severe ascites.
5.There is no evidence of carcinomatous meningitis, symptomatic brain metastases, or spinal metastases requiring surgical intervention.
6.20 years or older.
7.The ECOG Performance status(PS) is either 0 or 1.
8.Measurable lesions are present.
9.Refractory or intolerant to treatment, including Gemcitabine.
10.Within 14 days prior to enrollment, the subject has not received systemic steroid therapy in excess of equivalent to 10 mg daily of prednisolone or immunosuppressive drugs.
11.Has not received anticancer drugs within 14 days before enrollment or any other investigational drugs within 21 days before enrollment.
12.Not undergoing surgery within 28 days prior to enrollment.
13.Has not received radiation therapy within 28 days prior to enrollment.
14.Left ventricular ejection fraction (LVEF) of > 50%.
15.The most recent test values within 14 days before enrollment meet all of the following:
1)Neutrophil count ≧ 1,500/mm3
2)Hemoglobin ≧ 9.0 g/dL
3)Platelet count ≧ 100,000/mm3
4)Total Bilirubin ≦ 1.5 mg/dL
5)AST ≦ 100 IU/L
6)ALT ≦ 100 IU/L
7)Creatinine clearance ≧ 30 mL/min
16.They have agreed to a contraceptive at least 4.5 months after the last administration of the investigational product.
17.Written informed consent.

1.Having an active double cancer
2.Having a history/complication of symptomatic congestive heart failure within 6 months prior to enrollment or serious arrhythmias requiring treatment
3.Having a history/complication of myocardial infarction or unstable angina within 6 months prior to enrollment
4.Corrected QT interval (QTcF) > 470 ms (women) or QTcF > 450 ms (men) on 12-lead ECG
5.Having non-infectious interstitial lung disease or pneumonitis requiring steroid therapy. Complicated by interstitial lung disease or pneumonitis. Or these lung diseases cannot be ruled out by imaging during the screening period
6.Having uncontrolled infections that requiring IV injection of antibiotics, antivirals, or antifungal drugs
7.Positive for HIV antibodies, HTLV-1 antibodies, HBsAg, or HCV antibodies
8.Negative for HBsAg, positive for anti-HBs or anti-HBc, and positive HBV-DNA assay
9.Adverse events considered related to prior therapy that are not recovered to Grade 1 or less except alopecia
10.Hypersensitivity to the active ingredient of the investigational product has been confirmed
11.Women who are pregnant, breastfeeding, or who may be pregnant
12.Combined psychosis or psychiatric symptoms that are considered difficult to participate in the study
13.Because of drug allergy, neither iodine nor gadolinium drugs can be used.

Both

HER2 positive biliary tract cancer

Intervention type:DRUG Name of intervention:DS-8201a Dose form / Japanese Medical Device Nomenclature:INJECTION Route of administration / Site of application:INTRAVENOUS DRIP Dose per administration:5.4 mg/kg Dosing frequency / Frequency of use:OTHER, SPECIFY every 3weeks Planned duration of intervention:Until patient meets protocol treatment discontinuation criteria Intended dose regimen:DS-8201a monotherapy detailes of teratment arms:Patients are administered DS-8201a monotherapy 5.4mg/kg, every 3 week, until they meet treatment discontinuation criteria Comparative intervention name: Dose form / Japanese Medical Device Nomenclature: Route of administration / Site of application: Dose per administration: Dosing frequency / Frequency of use: Planned duration of intervention: Intended dose regimen:

Overall response rate in HER2 3+(IHC), or HER2 2+(IHC) and ISH positive patients by central imaging review

1)Overall response rate in all HER2-expressing patients by central imaging review
2)Overall response rate in HER2 low expressing patients by central imaging review
3)Overall response rate by local investigator review
4)Disease control rate
5)Progression-free survival
6)Overall survival
7)Incidence of adverse events

April. 10, 2019