Study to Evaluate Adverse Events, Optimal Dose, and Change in Disease Activity, With Livmoniplimab in Combination With Budigalimab Plus Chemotherapy Versus IV Infused Pembrolizumab Plus Chemotherapy in Adult Participants With Untreated Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (LIVIGNO-4)

A Randomized, Phase 2/3 Study to Evaluate the Optimal Dose, Safety, and Efficacy of Livmoniplimab in Combination With Budigalimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Untreated Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Non-Squamous Non-Small Cell Lung Cancer (NSCLC) remains a leading cause of cancer mortality worldwide, with poor survival prospects for metastatic disease. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab plus chemotherapy versus pembrolizumab plus chemotherapy in participants with untreated metastatic non-squamous non-small cell lung cancer.

Livmoniplimab is an investigational drug being developed for the treatment of NSCLC. There are 2 stages to this study. In Stage 1, there are 4 treatment arms. Participants will either receive livmoniplimab (at different doses) in combination with budigalimab (another investigational drug) + chemotherapy, budigalimab +chemotherapy, or pembrolizumab +chemotherapy. In Stage 2, there are 2 treatments arms. Participants will either receive livmoniplimab (optimized dose) in combination with budigalimab +chemotherapy or placebo in combination with pembrolizumab +chemotherapy. Chemotherapy consists of IV Infused pemetrexed + IV infused cisplatin or IV infused or injected carboplatin. Approximately 840 adult participants will be enrolled in the study across 200 sites worldwide.

Stage 1: In cohort 1, participants will receive intravenously (IV) infused livmoniplimab (dose A)+ IV infused budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + IV Infused pemetrexed. In cohort 2, participants will receive livmoniplimab (dose B) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. In cohort 3, participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed . In cohort 4, participants will receive IV Infused pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 2: In arm 1, participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. In arm 2, participants will receive IV Infused placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. The estimated study duration is 55 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Budigalimab; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Pemetrexed; Drug: Livmoniplimab; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 840
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Recruiting
      • Canberra Hospital /ID# 261891
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Recruiting
      • Nepean Hospital /ID# 262157
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital /ID# 261894
• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • AZ Maria Middelares /ID# 262313
  • Namur, Belgium, 5000
    • Recruiting
    • UCL Namur University Hospital, Site Sainte-Elisabeth /ID# 262557
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Recruiting
      • Universitair Ziekenhuis Antwerpen /ID# 261270
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1200
      • Recruiting
      • Cliniques Universitaires UCL Saint-Luc /ID# 261267
  • Hainaut
    • La Louvière, Hainaut, Belgium, 7100
      • Recruiting
      • Hospital La Louviere Site Jolimont - Helora /ID# 261269
  • Liege
    • Liège, Liege, Belgium, 4000
      • Recruiting
      • Groupe Sante CHC - Clinique du MontLegia /ID# 262338
• Chile
  • Santiago, Chile, 7501504
    • Recruiting
    • Hospital Clinico Universidad De Los Andes /ID# 262665
  • Region Metropolitana Santiago
    • Vitacura, Region Metropolitana Santiago, Chile, 7650027
      • Recruiting
      • Oncored /Id# 261801
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2520598
      • Recruiting
      • Sociedad Cem-Cancer Spa /Id# 262316
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4810218
      • Recruiting
      • Centro de Investigacion y Desarrollo Oncologico /ID# 261800
  • Santiago Metropolitan
    • Providencia, Santiago Metropolitan, Chile, 7500921
      • Recruiting
      • Fundacion Arturo Lopez Perez /ID# 261700
• France
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13015
      • Recruiting
      • APHM - Hopital Nord /ID# 261129
  • Isere
    • La Tronche, Isere, France, 38700
      • Recruiting
      • CHU Grenoble - Hopital Michallon /ID# 261131
  • Paris
    • Paris, Paris, France, 75248
      • Recruiting
      • Institut Curie /ID# 261127
  • Rhone
    • Bron, Rhone, France, 69500
      • Recruiting
      • Hospices Civils de Lyon (HCL) - Hopital Louis Pradel /ID# 261644
  • Val-de-Marne
    • Créteil, Val-de-Marne, France, 94000
      • Recruiting
      • Centre Hosp Intercommunal de Creteil /ID# 261130
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus /ID# 262431
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Recruiting
      • Shaare Zedek Medical Center /ID# 262432
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 261923
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Recruiting
      • Saitama Prefectural Cancer Center /ID# 262703
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital /ID# 261925
• Netherlands
  • Gelderland
    • Harderwijk, Gelderland, Netherlands, 3844 DG
      • Recruiting
      • Ziekenhuis St. Jansdal /ID# 261193
  • Limburg
    • Heerlen, Limburg, Netherlands, 6419 PC
      • Recruiting
      • Zuyderland Medisch Centrum /ID# 261190
  • Overijssel
    • Zwolle, Overijssel, Netherlands, 8025 AB
      • Recruiting
      • Isala /ID# 262458
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Pan American Center for Oncology Trials /ID# 269666
• Spain
  • Barcelona, Spain, 08017
    • Recruiting
    • UOMi Cancer Center - Clinica Tres Torres /ID# 262116
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall de Hebron /ID# 262113
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Maranon /ID# 262114
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre /ID# 262112
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia /ID# 262115
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Recruiting
      • Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 262723
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 262118
• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital /ID# 262016
  • Taipei, Taiwan, 104
    • Recruiting
    • Mackay Memorial Hospital /ID# 262534
  • Taipei, Taiwan, 11031
    • Recruiting
    • Taipei Medical University Hospital /ID# 262020
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Linkou Chang Gung Memorial Hospital /ID# 262535
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06560
    • Recruiting
    • Gazi University Medical Faculty /ID# 261786
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara City Hospital /ID# 261785
  • Izmir, Turkey (Türkiye), 35110
    • Recruiting
    • Dr. Suat Seren Gogus Has /ID# 261789
• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Moores Cancer Center /ID# 267782
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Recruiting
      • Memorial Hospital West /ID# 262221
    • Winter Haven, Florida, United States, 33880
      • Recruiting
      • Bond Clinic /ID# 262611
      • Contact: Site Coordinator; Phone Number: 863-293-1191 ex 3790
  • Georgia
    • Athens, Georgia, United States, 30607
      • Recruiting
      • University Cancer & Blood Cent /ID# 261824
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • Recruiting
      • The University of Chicago Medical Center /ID# 262259
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Medical Center /ID# 263196
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Recruiting
      • Baptist Health Lexington /ID# 261823
  • Michigan
    • Grand Rapids, Michigan, United States, 49546-7062
      • Recruiting
      • Cancer & Hematology Centers of Western Michigan - East /ID# 261826
      • Contact: Site Coordinator; Phone Number: 616-975-3065
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University-School of Medicine /ID# 262759
  • New York
    • Stony Brook, New York, United States, 11794-0001
      • Recruiting
      • Stony Brook Cancer Center /ID# 261954
  • North Carolina
    • Greensboro, North Carolina, United States, 27403-1109
      • Recruiting
      • Cone Health Cancer Center /ID# 262583
  • Ohio
    • Cincinnati, Ohio, United States, 45252
      • Recruiting
      • Oncology Hematology Care, Inc - Blue Ash /ID# 262733
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Recruiting
      • Guthrie Robert Packer Hospital /ID# 262758
  • Texas
    • El Paso, Texas, United States, 79915-1803
      • Completed
      • Renovatio clinical /ID# 262000
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital /ID# 262722
    • Plano, Texas, United States, 75075
      • Recruiting
      • Texas Oncology - Plano East /ID# 264356
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Texas Oncology - San Antonio Medical Center - Research Drive /ID# 264311
    • The Woodlands, Texas, United States, 77380-3181
      • Completed
      • Renovatio Clinical /ID# 261999
  • Washington
    • Olympia, Washington, United States, 98506-5028
      • Recruiting
      • Vista Oncology - East Olympia /ID# 262303

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of histologically or cytologically confirmed metastatic nonsquamous non-small cell lung cancer (NSCLC) with no known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) mutation, or other genomic aberration for which a locally approved targeted therapy is available.
• Must have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 as determined by the local site Investigator/radiology assessment.
• Life expectancy of at least 3 months and adequate organ function.

Exclusion Criteria:

- Received prior systemic therapy for the treatment of metastatic NSCLC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1 (Cohort 1): Livmoniplimab Dose A; Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.	Drug: Budigalimab; IV Infusion; Other Names: ABBV-181; Drug: Carboplatin; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Livmoniplimab; Intravenously (IV) Infusion; Other Names: ABBV-151; Drug: Carboplatin; IV Injection
Experimental: Stage 1 (Cohort 2): Livmoniplimab Dose B; Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.	Drug: Budigalimab; IV Infusion; Other Names: ABBV-181; Drug: Carboplatin; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Livmoniplimab; Intravenously (IV) Infusion; Other Names: ABBV-151; Drug: Carboplatin; IV Injection
Experimental: Stage 1 (Cohort 3): Budigalimab; Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.	Drug: Budigalimab; IV Infusion; Other Names: ABBV-181; Drug: Carboplatin; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Carboplatin; IV Injection
Experimental: Stage 1 (Cohort 4): Pembrolizumab; Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.	Drug: Carboplatin; IV Infusion; Drug: Pembrolizumab; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Carboplatin; IV Injection
Experimental: Stage 2 (Arm 1): Livmoniplimab (Dose Optimized); Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.	Drug: Budigalimab; IV Infusion; Other Names: ABBV-181; Drug: Carboplatin; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Livmoniplimab; Intravenously (IV) Infusion; Other Names: ABBV-151; Drug: Carboplatin; IV Injection
Experimental: Stage 2 (Arm 2): Placebo; Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.	Drug: Carboplatin; IV Infusion; Drug: Pembrolizumab; IV Infusion; Drug: Cisplatin; IV Infusion; Drug: Pemetrexed; IV Infusion; Drug: Carboplatin; IV Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR)	BOR of CR/PR is defined as achieving CR or PR according to response evaluation criteria in solid tumors (RECIST) v1.1 as determined by investigators at any time prior to subsequent anticancer therapy. Objective response rate (ORR), defined as the percentage of participants with a BOR of CR/PR, will be summarized.	Up to 21 Months
Stage 2: Overall Survival (OS)	OS is defined as the time measured from randomization until death from any cause.	Up to 55 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Progression Free Survival (PFS)	PFS is defined as the time measured from randomization until the first documentation of progressive disease (PD) according to RECIST 1.1 as determined by investigators or death from any cause, whichever occurs first.	Up to 21 Months
Stage 1: Duration of Response (DOR)	DOR is defined as the time from first CR/PR until the first documentation of PD according to RECIST 1.1 as determined by investigators or death from any cause, whichever occurs first.	Up to 21 Months
Stage 1: OS	OS is defined as the time measured from randomization until death from any cause.	Up to 21 Months
Stage 2: PFS	PFS is defined as the time measured from randomization until the first documentation of progressive disease according to RECIST 1.1 as determined by blinded independent central review (BICR) or death from any cause, whichever occurs first.	Up to 55 Months
Stage 2: BOR of CR/PR	BOR of CR/PR is defined as achieving CR or PR according to RECIST 1.1 as determined by investigators at any time prior to subsequent anticancer therapy. ORR, defined as the percentage of participants with a BOR of CR/PR, will be summarized.	Up to 55 Months
Stage 2: Change from Baseline in Physical Functioning (PF) as measured by the PF domain of European Organization for Research Treatment of Cancer Quality of Life Questionnaire 17 (EORTC QLQ-F17)	The EORTC QLQ-F17, a shorter, 17-item version that includes only the functional scales and the Global Health Status / Quality of Life scale of the EORTC QLQ-C30. QLQ-F17 includes the Physical (PF), Role (RF), Emotional (EF), Cognitive (CF) and Social Functioning (SF) scales as well as the Global Health Status/Quality of Life (QL) scale in their original wording. Participants rate items on a 4 point scale ranging form 1 to 4 (1- Not at All, 2= A Little, 3 = Quite a Bit, and 4= Very Much).	Up to 55 Months
Stage 2: Change from Baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)	The NSCLC -SAQ scale with seven items assessing 5 symptoms of NSCLC (cough, pain, dyspnea, fatigue and poor appetites). The recall period is "over the last 7 days." Each item has a 5-point verbal rating scale from either 0 "No <symptom> at All" to 4 "Very severe <symptom>" or from 0 "Never" to 4 "Always," depending on the item's format.	Up to 55 Months
Stage 2: Change from Baseline in Quality of Life as Measured by the Global Health Status/Quality of Life Domain of the EORTC QLQ-F17	The EORTC QLQ-F17, a shorter, 17-item version that includes only the functional scales and the Global Health Status / Quality of Life scale of the EORTC QLQ-C30. QLQ-F17 includes the Physical (PF), Role (RF), Emotional (EF), Cognitive (CF) and Social Functioning (SF) scales as well as the Global Health Status/Quality of Life (QL) scale in their original wording. Participants rate items on a 4 point scale ranging form 1 to 4 (1- Not at All, 2= A Little, 3 = Quite a Bit, and 4= Very Much).	Up to 55 Months
Stage 2: PFS per Investigator	PFS is defined as the time measured from randomization until the first documentation of progressive disease according to RECIST 1.1 as determined by the investigator or death from any cause, whichever occurs first.	Up to 55 Months
Stage 1: BOR of CR/PR per Investigator	BOR of CR/PR is defined as achieving CR or PR according to RECIST 1.1 as determined by investigators. ORR, defined as the percentage of participants with a BOR of CR/PR, will be summarized.	Up to 21 Months
Stage 2: DOR	DOR is defined as the time from first CR/PR until the first documentation of PD according to RECIST 1.1 as determined by BICR or death from any cause, whichever occurs first.	Up to 55 Months
Stage 2: DOR per investigator	DOR is defined as the time from first CR/PR until the first documentation of PD according to RECIST 1.1 as determined by investigators or death from any cause, whichever occurs first.	Up to 55 Months

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: January 24, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Pembrolizumab; Chemotherapy; ABBV-181; Budigalimab; Livmoniplimab; ABBV-151; Untreated Metastatic Non-Squamous Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; pembrolizumab; budigalimab
• Other Study ID Numbers: M23-721; 2023-505773-32-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No