A Study of Zanidatamab in Japanese Subjects With Locally Advanced or Metastatic HER2-Expressing Cancers

JRCT ID: jRCT2031210161

Registered date:23/06/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Locally advanced (unresectable) and/or metastatic HER2-expressing cancer
• Date of first enrollment: 23/08/2021
• Target sample size: 48
• Study type: Interventional
• Intervention(s): Zanidatamab is administered intravenously as a single agent (monotherapy).

Outcome(s)

Primary Outcome

- Frequency of dose-limiting toxicities (DLTs)
- Frequency and severity of adverse events (AEs)
- Frequency of serious adverse events (SAEs) and deaths
- Frequency and severity of adverse events of special interest (AESIs)
- Frequency and severity of clinical laboratory abnormalities
- Frequency of electrocardiogram (ECG) abnormalities
- Frequency of left ventricular ejection fraction (LVEF) abnormalities
- Eastern Cooperative Oncology Group Performance Status (ECOG PS)
- Frequency of dose reductions of zanidatamab

Secondary Outcome

- Serum concentrations of zanidatamab as a function of time post-dosing
- PK parameters for single (first) dose and multiple doses
- Objective response rate (ORR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Duration of response (DOR)
- Disease control rate (DCR)
- Clinical benefit rate (CBR)
- Progression-free survival (PFS)
- Frequency, duration, and time of onset of anti-drug antibodies (ADA), neutralizing antibodies, and HER2 extracellular domain (ECD)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Disease Diagnosis: Any locally advanced (unresectable) and/or metastatic HER2-expressing (HER2 1+, 2+, or 3+ by IHC) cancer (including but not limited to gastroesophageal adenocarcinoma [GEA], biliary tract, breast, ovarian, colorectal, and non small cell lung) that has progressed after receipt of all therapies known to confer clinical benefit (unless ineligible to receive a specific therapy).
2. Male or female Japanese subjects, >= 20 years of age at the time of signing informed consent.
3. ECOG performance status 0 or 1
4. Adequate hepatic function, as follows:
a. Aspartate aminotransferase (AST) <= 2.5 x the upper limit of normal (ULN) per institutional values (if liver or bone metastases are present, <= 5 x ULN)
b. Alanine aminotransferase (ALT) <= 2.5 x ULN per institutional values (if liver or bone metastases are present, <= 5 x ULN)
c. Total bilirubin <= 1.5 x ULN per institutional values
5. Adequate renal function (serum creatinine <= 1.5 x ULN or calculated glomerular filtration rate > 50 mL/min)
6. Hematological function, as follows:
a. Absolute neutrophil count (ANC) >= 1.5 x 109/L
b. Platelet count >= 75 x 109/L
c. Hemoglobin >= 9 g/dL
d. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) < 1.5 x ULN
7. Left ventricular ejection fraction (LVEF) >= 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)
8. Evaluable disease (target or non-target lesions per RECIST version 1.1)
9. Able to provide a fresh formalin-fixed, paraffin-embedded (FFPE) tumor sample for retrospective central evaluation of HER2 status; archival tumor specimens may be used if it is collected <= 6 months prior to enrollment and there is no intervening HER2 targeted treatment, unless otherwise approved by the medical monitor. Study eligibility may be based on local or central read (using ASCO/CAP guidelines) of fresh or archived tumor biopsy; if local read is used for eligibility, archived or fresh FFPE biopsy must be provided for retrospective centralized review unless otherwise approved by the sponsor.
10. Female subjects of childbearing potential and male subjects with a partner of childbearing potential must be willing to use 2 methods of birth control with a failure rate of less than 1% per year during the study and for 7 months after the last dose of study drug. These include, but are not limited to, established use of oral contraceptives, or placement of intra-uterine device or intra-uterine system (as described in Section 4.3.2).
In addition, female subjects must agree not to donate oocytes, and male subjects must avoid sperm donation for the duration of the study and for 7 months after the last dose of study drug.
11. Signed informed consent prior to any study procedures, except prescreening for HER2 status.

Exclude criteria

1. Treatment with experimental therapies within 4 weeks before first zanidatamab dosing
2. Treatment with other cancer therapy not otherwise specified within 4 weeks before zanidatamab dosing
3.Treatment with anthracyclines within 90 days before first zanidatamab dosing or total lifetime dose exceeding 300 mg/m2 adriamycin or equivalent
4. Treatment with trastuzumab, pertuzumab, lapatinib, or T-DM1 within 3 weeks before the first zanidatamab dose
5. Untreated brain metastases, unless approved by the medical monitor (subjects with treated brain metastases who are off steroids and anticonvulsants and are stable for at least 1 month at the time of Screening are eligible). All breast cancer and GEA subjects should undergo screening for brain metastases prior to starting treatment. Those subjects found to have untreated brain metastases may be rescreened following appropriate therapy.
6. History of or ongoing leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI but is not suspected clinically by the investigator, the subject is eligible if he or she is free of neurological symptoms of LMD as documented by the investigator
7. Major surgery or radiotherapy within 3 weeks before the first zanidatamab dose
8. Pregnant or breast-feeding women. Women who are breastfeeding may be enrolled in the study if they cease breastfeeding for the duration of the study and for 7 months after completion of study treatment.
9. History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in drug formulation
10. Any other cancer within 3 years before the first zanidatamab dose with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin, or any other cancer that has undergone curative treatment, with approval from the sponsor medical monitor.
11. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of subjects with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
12. Peripheral neuropathy: > Grade 2 NCI-CTCAE version 4.03
13. Prior history of interstitial lung disease
14. History of noncompliance to medical regimens
15. Known active hepatitis B or C or known infection with human immunodeficiency virus (HIV). Subjects who are hepatitis B surface antigen [HBsAg] positive are eligible if they have hepatitis B virus (HBV) DNA less than 500 IU/mL or 2,500 copies/mL with monitoring and/or antiviral prophylaxis as appropriate.
16. Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible
17. Use of corticosteroids administered at doses equivalent to > 15 mg per day of prednisone within 2 weeks before zanidatamab dosing unless otherwise approved by the study medical monitor.
18. QTc Fridericia (QTcF) > 470 ms. Note: For subjects with longer QTcF on initial ECG, follow-up ECG may be performed in triplicate and the mean of the 3 values will be used to determine eligibility.
19. Any toxicity related to prior cancer therapies that has not resolved to <= Grade 1, with the following exceptions: alopecia; neuropathy (which must have resolved to <= Grade 2); and congestive heart failure (CHF), which must have been <= Grade 1 in severity at the time of occurrence and must have resolved completely; and Grade 2 hypothyroidism or panhypopituitarism related to treatment with immunotherapy (subject must be on a stable dose of hormone replacement therapy).
20. Clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic CHF.
21. Known myocardial infarction or unstable angina within 6 months before the first zanidatamab dose.

Related Information

• Primary Sponsor: Rajen Oza