Study Evaluating Effectiveness and Safety of Zimberelimab and Domvanalimab in Lung Cancer

Phase 2

Active, not recruiting

• Conditions: Squamous Non Small Cell Lung Cancer; Non Small Cell Lung Cancer; Nonsquamous Non Small Cell Lung Cancer; Lung Cancer
• Interventions: Drug: Domvanalimab; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Zimberelimab; Drug: Paclitaxel; Drug: Pemetrexed

• Registration Number: NCT04736173
• Lead Sponsor: Arcus Biosciences, Inc.

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-29
• Study First Submitted QC: 2021-01-29
• Study First Posted: 2021-02-03
• Study Start: 2021-02-08
• Status Verified: 2024-11
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-27
• Primary Completion: 2027-05
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 169

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)	Domvanalimab	Participants will receive zimberelimab in combination with AB154 by IV infusion.
Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)	Domvanalimab	Participants will receive domvanalimab in combination with zimberelimab by IV infusion.
Arm A - Study Part 1 (Platinum-based Chemotherapy)	Carboplatin	Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.
Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)	Zimberelimab	Participants will receive zimberelimab in combination with AB154 by IV infusion.
Arm B - Study Part 1 (Zimberelimab Monotherapy)	Zimberelimab	Participants will receive zimberelimab monotherapy by IV infusion.
Arm A - Study Part 1 (Platinum-based Chemotherapy)	Paclitaxel	Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.
Arm A - Study Part 1 (Platinum-based Chemotherapy)	Pemetrexed	Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.
Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)	Zimberelimab	Participants will receive domvanalimab in combination with zimberelimab by IV infusion.
Arm E - Study Part 2 (Pembrolizumab)	Pembrolizumab	Participants will receive pembrolizumab by IV infusion.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	From randomization until death from any cause (up to 7 years)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With treatment-emergent adverse events	From randomization until death from any cause (up to 7 years)
Confirmed Overall Response Rate (ORR)	From randomization until death from any cause (up to 7 years)
Overall Survival (OS)	From randomization until death from any cause (up to 7 years)

Trial Locations

Locations (91)

Hope and Healing Cancer Service; 🇺🇸 Hinsdale, Illinois, United States

University General Hospital "Attikon"; 🇬🇷 Chaidari, Greece

Humanity and Health Clinical Trial Centre; 🇭🇰 Hong Kong, Hong Kong

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

General hospital of Athens, chest diseases Sotiria; 🇬🇷 Athens, Greece

General Oncology Hospital of Kifissia " Agioi Anargyroi"; 🇬🇷 Kifissia, Greece

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

Cha University Bundang Medical Center; 🇰🇷 Seongnam, Korea, Republic of

Gangnam Severance Hospital Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea Eunpyeong St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

General Hospital of Patra Agios Andreas; 🇬🇷 Patras, Greece

Dong-A University Hospital; 🇰🇷 Busan, Korea, Republic of

Kosin University Gospel Hospital; 🇰🇷 Busan, Korea, Republic of

The Catholic University of Korea Incheon St. Mary's Hospital; 🇰🇷 Incheon, Korea, Republic of

Gyeongsang National University Hospital; 🇰🇷 Jinju, Korea, Republic of

Hong Kong Integrated Oncology Centre; 🇭🇰 Hong Kong, Hong Kong

Hong Kong United Oncology Centre; 🇭🇰 Hong Kong, Hong Kong

Princess Margaret Hospital; 🇭🇰 Hong Kong, Hong Kong

Jeonbuk National University Hospital; 🇰🇷 Jeonju, Korea, Republic of

Inha University Hospital; 🇰🇷 Incheon, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

Ajou University Hospital.; 🇰🇷 Suwon, Korea, Republic of

The Catholic University of Korea St. Vincent Hospital; 🇰🇷 Suwon, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Korea, Republic of

Hospital Sultan Ismail; 🇲🇾 Johor Bahru, Malaysia

Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

Pantai Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

Universiti Kebangsaan Malaysia Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan; 🇲🇾 Kuantan, Malaysia

Hospital Umum Sarawak; 🇲🇾 Kuching, Malaysia

Hospital Pulau Pinang; 🇲🇾 Pulau Pinang, Malaysia

Mount Miriam Cancer Hospital; 🇲🇾 Pulau Pinang, Malaysia

Institut Kanser Negara; 🇲🇾 Putrajaya, Malaysia

Health Pharma Professional Research; 🇲🇽 Benito Juarez, Mexico

Hospital Civil Fray Antonio Alcalde; 🇲🇽 Guadalajara, Mexico

Chong Hua Hospital; 🇵🇭 Cebu, Philippines

Metro Davao Medical and Research Centre; 🇵🇭 Davao City, Philippines

Makati Medical Centre; 🇵🇭 Manila, Philippines

Philippine General Hospital; 🇵🇭 Manila, Philippines

St. Luke Medical Centre Quezon City; 🇵🇭 Quezon City, Philippines

Exellentis Clinical Trial Consultants; 🇿🇦 George, South Africa

Cancercare PE; 🇿🇦 Johannesburg, South Africa

The Medical Oncology Centre of Rosebank; 🇿🇦 Johannesburg, South Africa

Wits Clinical Research CMJAH Clinical Trial Site; 🇿🇦 Johannesburg, South Africa

Port Elizabeth Oncology Centre-Cancercare; 🇿🇦 Port Elizabeth, South Africa

University of Pretoria Medical Oncology; 🇿🇦 Pretoria, South Africa

Wilgers Oncology Centre; 🇿🇦 Pretoria, South Africa

Chang Gung Medical Foundation Kaohsiung; 🇨🇳 Kaohsiung City, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung City, Taiwan

China Medical University Hospital; 🇨🇳 Taichung City, Taiwan

Chung Shan Medical University Hospital; 🇨🇳 Taichung City, Taiwan

Taipei Medical University Hospital; 🇨🇳 Taipei, Taiwan

King Chulalongkorn Memorial Hospital; 🇹🇭 Bangkok, Thailand

Phramongkutklao Hospital; 🇹🇭 Bangkok, Thailand

Police General Hospital; 🇹🇭 Bangkok, Thailand

Rajavithi Hospital; 🇹🇭 Bangkok, Thailand

Siriraj Hospital; 🇹🇭 Bangkok, Thailand

Vajira Hospital; 🇹🇭 Bangkok, Thailand

Prapokklao Hospital; 🇹🇭 Chanthaburi, Thailand

Maharaj Nakorn Chiang Mai Hospital; 🇹🇭 Chiang Mai, Thailand

Nakornping Hospital; 🇹🇭 Chiang Mai, Thailand

Srinagarind Hospital; 🇹🇭 Khon Kaen, Thailand

Lampang Hospital; 🇹🇭 Lampang, Thailand

HRH Princess Maha Chakri Sirindhorn Medical Centre; 🇹🇭 Nakhon Nayok, Thailand

Maharat Nakhon Ratchasima Hospital; 🇹🇭 Nakhon Ratchasima, Thailand

Buddhachinaraj Phitsanulok Hospital; 🇹🇭 Phitsanulok, Thailand

Naresuan University Hospital; 🇹🇭 Phitsanulok, Thailand

Saraburi Hospital; 🇹🇭 Saraburi, Thailand

Songkhlanagarind Hospital; 🇹🇭 Songkhla, Thailand

Sunpasitthiprasing Hospital; 🇹🇭 Ubon Ratchathani, Thailand

Udon Thani Hospital; 🇹🇭 Udon Thani, Thailand

Adana City Hospital; 🇹🇷 Adana, Turkey

Ankara City Hospital; 🇹🇷 Adana, Turkey

Gazi University Medical Faculty; 🇹🇷 Cankaya, Turkey

Memorial Ankara Hospital; 🇹🇷 Ankara, Turkey

Trakya University Medical Faculty; 🇹🇷 Edirne, Turkey

Acibadem Atakent Hospital; 🇹🇷 Istanbul, Turkey

Goztepe Prof. Dr. Suleyman Yalcin City Hospital; 🇹🇷 Istanbul, Turkey

Medipol University Medical Facility; 🇹🇷 Istanbul, Turkey

Medipol University Medical Faculty; 🇹🇷 Istanbul, Turkey

Kocaeli Universitesi Tip Fakultesi; 🇹🇷 Kocaeli, Turkey

Kocaeli Universitiesi Tip Fakultesi; 🇹🇷 Kocaeli, Turkey

Dicle University, Medical faculty; 🇹🇷 Sur, Turkey

103 Military Hospital; 🇻🇳 Hanoi, Vietnam

National Lung Hospital; 🇻🇳 Hanoi, Vietnam

Hue Central Hospital; 🇻🇳 Hue, Vietnam