Phase 3 Study Comparing Zimberelimab with Domvanalimab to Pembrolizumab in Advanced Non-Small Cell Lung Cancer

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

31 Aug 2023 → 10 Jan 2025

Decision date (initial)

2023-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc. · Arcus Biosciences, Inc.

External identifiers

EU CT number

2022-503071-28-00

EudraCT number

2020-003562-39

ClinicalTrials.gov

NCT04736173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the efficacy of zimberelimab and domvanalimab combination therapy compared to pembrolizumab in OS (Arm D vs Arm E)

Secondary objectives 3

1. To evaluate the efficacy of zimberelimab and domvanalimab combination therapy compared to pembrolizumab in PFS and ORR (Arm D vs Arm E)
2. To assess the safety of zimberelimab and domvanalimab combination therapy compared to pembrolizumab (Arm D vs Arm E)
3. To compare the effect of zimberelimab and domvanalimab relative to pembrolizumab (Arm D vs Arm E) on health-related QOL using NSCLCSAQ

Conditions and MedDRA coding

Squamous Non-small cell Lung Cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically confirmed, treatment naïve, locally advanced or metastatic (stage IIIB IV per AJCC version 8), squamous or non-squamous NSCLC with documented high PD L1 expression (TC ≥ 50%) as determined by the VENTANA SP263 IHC assay, as assessed by central laboratories).
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
3. Must have at least 1 measurable lesion per RECIST v1.1
4. Adequate organ and marrow function
5. If a participant has brain or meningeal metastases, the participant must meet the following criteria: a. Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose, b) Participants with previously treated brain metastases may participate provided they have stable central nervous system (CNS) disease for at least 4 weeks prior to enrollment, c) Stable CNS disease is defined as resolution of all neurologic symptoms to baseline, having no evidence of new or enlarging brain metastases, and not requiring use of corticosteroids for CNS disease for at least 14 days prior to the start of study treatment. Participants who have had brain metastases resected or have received whole brain radiotherapy ending at least 4 weeks (or stereotactic radiotherapy ending at least 2 weeks) prior to initiation of study treatment are permitted d) Carcinomatous meningitis is excluded regardless of clinical stability

Exclusion criteria 5

1. Presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved by local health authority and available
2. Use of any live vaccines against infectious diseases within 28 days of first dose
3. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
4. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer
5. Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an immune checkpoint

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 3

1. PFS according to RECIST v1.1 by blinded independent central review, and confirmed ORR according to RECIST v1.1 as assessed by BICR.
2. Presence of treatment-emergent adverse events, and Changes in vital signs measurements and clinical laboratory parameters
3. Time to first symptom deterioration in NSCLC-SAQ total score

Investigational products

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

Test 2

Comparator 1

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 15

Sponsor responsibilities

Article 77 compliance

Arcus Biosciences Inc.

Contact point sponsor

Arcus Biosciences Inc.

Article 77 implementation

Arcus Biosciences Inc.

Locations

4 EU/EEA countries · 21 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 1 file

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

Application history

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