A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jazz Pharmaceuticals Ireland Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Oct 2021 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Jazz Pharmaceutical Ireland Ltd

External identifiers

EU CT number

2023-510319-20-00

EudraCT number

2021-000296-36

ClinicalTrials.gov

NCT05152147

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Pharmacodynamic, Efficacy

To compare the efficacy of zanidatamab in combination with chemotherapy or in combination with chemotherapy and tislelizumab to the efficacy of trastuzumab in combination with chemotherapy in subjects with unresectable locally advanced, recurrent or metastatic HER2 positive GEA

Secondary objectives 1

1. ●To further compare the efficacy of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab to chemotherapy with trastuzumab ● To assess contribution of components of tislelizumab in combination with zanidatamab and chemotherapy ● To evaluate the safety and tolerability of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ●To evaluate the effect of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab on health-related quality of life (HRQoL) ●To evaluate the pharmacokinetics (PK) of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ●To evaluate the PK of tislelizumab in combination with chemotherapy and zanidatamab ●To evaluate the immunogenicity of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ●To evaluate the immunogenicity of tislelizumab in combination with chemotherapy and zanidatamab

Conditions and MedDRA coding

Gastroesophageal Adenocarcinoma (GEA)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISHpositivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment. 2.Assessable (measurable or non-measurable) disease as defined by RECIST 1.1. 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization 4.Adequate organ function 5.Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)

Exclusion criteria 1

1. 1.Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA. 2.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 3. Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unrespectable locally advanced, recurrent or metastatic GEA. 4.Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are completely off steroids and anticonvulsantsand are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization). 5.Known history of or ongoing leptomeningeal disease (LMD). 6.Known additional malignancy that is not considered cured or that has required treatment within the past 3 years. 7.Known active hepatitis 8.Any history of human immunodeficiency virus (HIV) infection 9.Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible 10.Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). 11.QTc Fridericia (QTcF) > 470 ms.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. ●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
2. ●Overall survival (OS) The primary PFS analysis will be performed once the target event count has been reached for each comparison. This is estimated to occur 7 months after the last subject is randomized. At this time, interim analyses of OS will be performed.

Secondary endpoints 6

1. ●Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR
2. ●Duration of response (DOR) by RECIST 1.1, assessed by BICR
3. ●PFS by RECIST 1.1, per investigator assessment
4. ●Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters
5. ●Serum concentration and PK parameters for zanidatamab
6. ●Serum concentrations for tislelizumab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jazz Pharmaceuticals Ireland Limited

Sponsor organisation

Jazz Pharmaceuticals Ireland Limited

Address

5th Floor, Waterloo Exchange, Waterloo Road Waterloo Exchange Waterloo Road

City

Dublin 4

Postcode

D04 E5W7

Country

Ireland

Scientific contact point

Organisation

Jazz Pharmaceuticals Ireland Limited

Contact name

Medical Monitor

Public contact point

Organisation

Jazz Pharmaceuticals Ireland Limited

Contact name

Medical Monitor

Third parties 16

Locations

12 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 144 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications