A safety and efficacy study of treatment combinations with and without chemotherapy in adult patients with advanced upper gastrointestinal tract malignancies

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

13 Sep 2022 → ongoing

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511917-40-00

EudraCT number

2021-006291-16

ClinicalTrials.gov

NCT05329766

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To assess the safety and tolerability of domvanalimab, zimberelimab, and quemliclustat-based combinations in participants with locally advanced unresectable or metastatic gastric, GEJ, and esophageal adenocarcinoma.

To assess the clinical activity of domvanalimab, zimberelimab, and quemliclustat-based combinations in participants with locally advanced unresectable or metastatic gastric, GEJ, and esophageal adenocarcinoma.

Secondary objectives 3

1. To assess the clinical activity of the study treatment in each cohort according to PD-L1 expression.
2. To describe the pharmacokinetic (PK) profile of domvanalimab, zimberelimab, and quemliclustat in combinations with and without chemotherapy.
3. To describe immunogenic responses to domvanalimab and zimberelimab in immunotherapy-based combinations.

Conditions and MedDRA coding

Advanced Upper Gastrointestinal Tract Malignancies

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3 months as assessed by the Investigator
2. Eastern cooperative oncology group (ECOG) Performance Score of 0-1
3. At least one measurable target lesion per RECIST v1.1.
4. Adequate organ and marrow function
5. Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing

Exclusion criteria 5

1. Participants with underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational products hazardous
2. Only for Cohort A: Known Human Epidermal Growth Factor Receptor 2 (HER-2) positive tumor
3. Known untreated, symptomatic, or actively progressing central nervous system (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
4. Discontinued use of prior immune checkpoint therapy due to immune related adverse events; received prior treatment with an anti-TIGIT monoclonal antibody.
5. History of trauma or major surgery within 28 days prior to enrollment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and any Clinically meaningful trends in safety parameters [Time Frame: Up to 18 months]
2. Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and assessed by the investigator [Time Frame: Up to 18 months]

Secondary endpoints 10

1. Objective Response Rate (ORR) as measured by PD-L1 Expression Level [Time Frame: Up to 18 months]
2. Overall survival (OS) [Time Frame: From date of first dose until the date of death due to any cause (approximately 18 months)]
3. Progression-free survival (PFS) as determined by the Investigator according to RECIST v1.1 [Time Frame: Up to 18 months]
4. Disease Control (complete response, partial response, or stable disease) for greater than equal to 12 weeks [Time Frame: Up to 18 months]
5. Duration of response (DOR) as determined by the Investigator according to RECIST v1.1 [Time Frame: Up to 18 months]
6. Plasma concentration of domvanalimab [Time Frame: Up to 18 months]
7. Plasma concentration of zimberelimab [Time Frame: Up to 18 months]
8. Plasma concentration of quemliclustat [Time Frame: Up to 18 months]
9. Percentage of participants with anti-drug antibodies to domvanalimab [Time Frame: Up to 18 months]
10. Percentage of participants with anti-drug antibodies to zimberelimab [Time Frame: Up to 18 months]

Investigational products

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

Test 3

Auxiliary 3

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 3

Locations

1 EU/EEA country · 12 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 11 files

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

Application history

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