A phase 3 clinical trial of a new combination treatment, domvanalimab and zimberelimab, plus chemotherapy, for people with an upper gastrointestinal tract cancer that cannot be removed with surgery that has spread to other parts of the body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arcus Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2023 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507522-16-00

EudraCT number

2022-002222-27

ClinicalTrials.gov

NCT05568095

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Pharmacokinetic, Therapy, Pharmacodynamic, Efficacy, Pharmacogenomic

1. To compare overall survival (OS) of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with high programmed death ligand 1 (PD-L1) expression.
2. To compare OS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with positive PD-L1 expression.
3. To compare OS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in all randomized participants.

Secondary objectives 6

1. To compare PFS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with high PD-L1 expression
2. To compare PFS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with positive PD-L1 expression.
3. To compare PFS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in all randomized participants
4. To assess the disease-related symptoms and impact of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy using the Functional Assessment of Cancer Therapy – Gastric (FACT-Ga) in participants with high PD-L1 expression, positive PD-L1 expression, and in all randomized participants.
5. To assess additional measures of clinical activity in participants with high PD-L1 expression, positive PD-L1 expression, and in all randomized participants.
6. To assess the safety and tolerability of domvanalimab + zimberelimab + chemotherapy in all randomized participants

Conditions and MedDRA coding

Metastatic Esophageal or Gastric Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age >= 18 years at the time of signing the informed consent.
2. Capable of giving signed informed consent which is in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.
3. Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
4. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
5. At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Exclusion criteria 5

1. Underlying medical or psychiatric conditions that, in the investigator's or sponsor's opinion, will make the administration of study-specified therapy hazardous, including but not limited to: 1. Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization, 2. Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization, 3. History of prior solid-organ transplantation, including allogenic bone marrow transplantation, 4. Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial.
2. Known human epidermal growth factor receptor 2 (HER-2) positive tumor.
3. Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
4. Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
5. Disease progression within 6 months of neoadjuvant or adjuvant chemotherapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS is defined as the length of time from date of randomization until the date of death from any cause

Secondary endpoints 5

1. PFS is defined as the time from date of randomization until disease progression or death from any cause, whichever comes first, as measured per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the investigator
2. Time to first symptom deterioration in the FACT-Ga gastric cancer subscale.
3. Objective response rate (ORR) is defined as the proportion of participants who have achieved confirmed complete response (CR) or confirmed partial response (PR) to study therapy as assessed by the investigator according to RECIST 1.1
4. Duration of response (DOR) is measured from the time of first confirmed response (CR or PR as measured by RECIST v1.1) as assessed by the investigator, until the date of first documented disease progression or death, whichever comes first.
5. 5. The incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and any clinically meaningful trends in safety parameters

Investigational products

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

Test 2

Comparator 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arcus Biosciences Inc.

Sponsor organisation

Arcus Biosciences Inc.

Address

3928 Point Eden Way

City

Hayward

Postcode

94545-3719

Country

United States

Scientific contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Public contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Third parties 17

Locations

9 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 80 files

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

Application history

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