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)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06236438
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 840
- 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.
- Received prior systemic therapy for the treatment of metastatic NSCLC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Stage 2 (Arm 2): Placebo Pemetrexed Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 1 (Cohort 2): Livmoniplimab Dose B Budigalimab Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 2): Livmoniplimab Dose B Carboplatin Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 3): Budigalimab Budigalimab Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed. Stage 1 (Cohort 2): Livmoniplimab Dose B Livmoniplimab Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 1): Livmoniplimab Dose A Carboplatin Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 2): Livmoniplimab Dose B Pemetrexed Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Pemetrexed Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 1): Livmoniplimab Dose A Livmoniplimab Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Livmoniplimab Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 1): Livmoniplimab Dose A Cisplatin Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Budigalimab Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 1): Livmoniplimab Dose A Budigalimab Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 1): Livmoniplimab Dose A Pemetrexed Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 4): Pembrolizumab Cisplatin Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 1 (Cohort 2): Livmoniplimab Dose B Cisplatin Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 1 (Cohort 3): Budigalimab Pemetrexed Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed. Stage 1 (Cohort 3): Budigalimab Cisplatin Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed. Stage 1 (Cohort 3): Budigalimab Carboplatin Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed. Stage 1 (Cohort 4): Pembrolizumab Pembrolizumab Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 1 (Cohort 4): Pembrolizumab Pemetrexed Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 1 (Cohort 4): Pembrolizumab Carboplatin Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Carboplatin Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 2 (Arm 2): Placebo Carboplatin Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 2 (Arm 2): Placebo Pembrolizumab Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed. Stage 2 (Arm 1): Livmoniplimab (Dose Optimized) Cisplatin Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed. Stage 2 (Arm 2): Placebo Cisplatin Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
- Primary Outcome Measures
Name Time Method Stage 1: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) Up to 21 Months 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.
Stage 2: Overall Survival (OS) Up to 55 Months OS is defined as the time measured from randomization until death from any cause.
- Secondary Outcome Measures
Name Time Method Stage 2: PFS per Investigator Up to 55 Months 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.
Stage 1: Progression Free Survival (PFS) Up to 21 Months 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.
Stage 1: Duration of Response (DOR) Up to 21 Months 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.
Stage 1: OS Up to 21 Months OS is defined as the time measured from randomization until death from any cause.
Stage 2: PFS Up to 55 Months 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.
Stage 2: DOR per investigator Up to 55 Months 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.
Stage 2: BOR of CR/PR Up to 55 Months 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.
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) Up to 55 Months 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).
Stage 2: Change from Baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Up to 55 Months 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.
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 Up to 55 Months 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).
Stage 1: BOR of CR/PR per Investigator Up to 21 Months 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.
Stage 2: DOR Up to 55 Months 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.
Trial Locations
- Locations (56)
Moores Cancer Center /ID# 267782
🇺🇸La Jolla, California, United States
Memorial Hospital West /ID# 262221
🇺🇸Pembroke Pines, Florida, United States
Bond Clinic /ID# 262611
🇺🇸Winter Haven, Florida, United States
University Cancer & Blood Cent /ID# 261824
🇺🇸Athens, Georgia, United States
The University of Chicago Medical Center /ID# 262259
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center /ID# 263196
🇺🇸Westwood, Kansas, United States
Baptist Health Lexington /ID# 261823
🇺🇸Lexington, Kentucky, United States
Cancer & Hematology Centers of Western Michigan - East /ID# 261826
🇺🇸Grand Rapids, Michigan, United States
Washington University-School of Medicine /ID# 262759
🇺🇸Saint Louis, Missouri, United States
Stony Brook Cancer Center /ID# 261954
🇺🇸Stony Brook, New York, United States
Cone Health Cancer Center /ID# 262583
🇺🇸Greensboro, North Carolina, United States
Oncology Hematology Care, Inc - Blue Ash /ID# 262733
🇺🇸Cincinnati, Ohio, United States
Guthrie Robert Packer Hospital /ID# 262758
🇺🇸Sayre, Pennsylvania, United States
Renovatio clinical /ID# 262000
🇺🇸El Paso, Texas, United States
Houston Methodist Hospital /ID# 262722
🇺🇸Houston, Texas, United States
Texas Oncology - Plano East /ID# 264356
🇺🇸Plano, Texas, United States
Texas Oncology, P. A. /ID# 264311
🇺🇸San Antonio, Texas, United States
Renovatio Clinical /ID# 261999
🇺🇸The Woodlands, Texas, United States
Vista Oncology - East Olympia /ID# 262303
🇺🇸Olympia, Washington, United States
The Canberra Hospital /ID# 261891
🇦🇺Garran, Australian Capital Territory, Australia
Nepean Hospital /ID# 262157
🇦🇺Kingswood, New South Wales, Australia
Westmead Hospital /ID# 261894
🇦🇺Westmead, New South Wales, Australia
Hospital La Louviere Site Jolimont - Helora /ID# 261269
🇧🇪La Louvière, Hainaut, Belgium
AZ Maria Middelares /ID# 262313
🇧🇪Gent, Belgium
Groupe Sante CHC - Clinique du MontLegia /ID# 262338
🇧🇪Liege, Belgium
UCL Namur University Hospital, Site Sainte-Elisabeth /ID# 262557
🇧🇪Namur, Belgium
Centro de Investigacion y Desarrollo Oncologico /ID# 261800
🇨🇱Temuco, Araucania, Chile
Fundacion Arturo Lopez Perez /ID# 261700
🇨🇱Providencia, Region Metropolitana De Santiago, Chile
Oncored /Id# 261801
🇨🇱Vitacura, Region Metropolitana Santiago, Chile
Sociedad Cem-Cancer Spa /Id# 262316
🇨🇱Viña del Mar, ValparaÃso, Chile
Hospital Clinico Universidad De Los Andes /ID# 262665
🇨🇱Santiago, Chile
APHM - Hopital Nord /ID# 261129
🇫🇷Marseille, Bouches-du-Rhone, France
CHU Grenoble - Hopital Michallon /ID# 261131
🇫🇷La Tronche, Isere, France
Centre Hosp Intercommunal de Creteil /ID# 261130
🇫🇷Creteil, Val-de-Marne, France
Rambam Health Care Campus /ID# 262431
🇮🇱Haifa, H_efa, Israel
Shaare Zedek Medical Center /ID# 262432
🇮🇱Jerusalem, Yerushalayim, Israel
National Cancer Center Hospital East /ID# 261923
🇯🇵Kashiwa-shi, Chiba, Japan
Saitama Cancer Center /ID# 262703
🇯🇵Kitaadachi-gun, Saitama, Japan
National Cancer Center Hospital /ID# 261925
🇯🇵Chuo-ku, Tokyo, Japan
Ziekenhuis St. Jansdal /ID# 261193
🇳🇱Harderwijk, Gelderland, Netherlands
Isala /ID# 262458
🇳🇱Zwolle, Overijssel, Netherlands
Pan American Center for Oncology Trials /ID# 269666
🇵🇷Rio Piedras, Puerto Rico
Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 262723
🇪🇸Santiago de Compostela, A Coruna, Spain
Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 262118
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
UOMi Cancer Center - Clinica Tres Torres /ID# 262116
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron /ID# 262113
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon /ID# 262114
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre /ID# 262112
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia /ID# 262115
🇪🇸Valencia, Spain
National Cheng Kung University Hospital /ID# 262016
🇨🇳Tainan, Taiwan
Mackay Memorial Hospital /ID# 262534
🇨🇳Taipei City, Taiwan
Taipei Medical University Hospital /ID# 262020
🇨🇳Taipei City, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 262535
🇨🇳Taoyuan City, Taiwan
Gazi University Medical Faculty /ID# 261786
🇹🇷Ankara, Turkey
Ankara City Hospital /ID# 261785
🇹🇷Ankara, Turkey
Dr. Suat Seren Gogus Has /ID# 261789
🇹🇷Izmir, Turkey