Study Evaluating Effectiveness and Safety of Zimberelimab and Domvanalimab in Lung Cancer (ARC-10)

Arcus Biosciences

Status and phase: Active, not recruiting; Phase 2

Conditions: Squamous Non Small Cell Lung Cancer; Nonsquamous Non Small Cell Lung Cancer; Lung Cancer; Non Small Cell Lung Cancer

Treatments: Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: Domvanalimab; Drug: Zimberelimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04736173

2020-003562-39 (EudraCT Number)

PHRR210222-003371 (Other Identifier)

2022-503071-28-00 (EU Trial (CTIS) Number)

ARC-10

Details and patient eligibility

About

This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC).

Enrollment: 169 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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).

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

• Must have at least 1 measurable lesion per RECIST v1.1

• Adequate organ and marrow function

• If a participant has brain or meningeal metastases, the participant must meet the following criteria:

  1. Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose.
  2. 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. 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.
  3. Carcinomatous meningitis is excluded regardless of clinical stability.

Key Exclusion Criteria:

• Presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved by local health authority and available
• Use of any live vaccines against infectious diseases within 28 days of first dose
• 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.
• 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
• Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an immune checkpoint.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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169 participants in 5 patient groups

Arm A - Study Part 1 (Platinum-based Chemotherapy)

Active Comparator group

Description:

Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pemetrexed

Arm B - Study Part 1 (Zimberelimab Monotherapy)

Experimental group

Description:

Participants will receive zimberelimab monotherapy by IV infusion.

Treatment:

Drug: Zimberelimab

Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)

Active Comparator group

Description:

Participants will receive zimberelimab in combination with AB154 by IV infusion.

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)

Experimental group

Description:

Participants will receive domvanalimab in combination with zimberelimab by IV infusion.

Treatment:

Drug: Zimberelimab

Drug: Domvanalimab

Arm E - Study Part 2 (Pembrolizumab)

Experimental group

Description:

Participants will receive pembrolizumab by IV infusion.

Treatment:

Drug: Pembrolizumab