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)

Phase 3RecruitingNCT06236438

AbbVie840 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (61)

UC San Diego Health - Moores Cancer Center /ID# 267782

La Jolla, California, United States

COMPLETED

Memorial Hospital West /ID# 262221

Pembroke Pines, Florida, United States

COMPLETED

Bond Clinic /ID# 262611

Winter Haven, Florida, United States

RECRUITING

University Cancer and Blood Cent /ID# 261824

Athens, Georgia, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 21 Months

Stage 2: Overall Survival (OS)

OS is defined as the time measured from randomization until death from any cause.

Time frame: Up to 55 Months

Secondary Outcomes

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.

Time frame: 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.

Time frame: Up to 21 Months

Stage 1: OS

OS is defined as the time measured from randomization until death from any cause.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 55 Months

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)

Overview

Conditions

Interventions

Eligibility

Locations (61)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts