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)
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- AbbVie
- Enrollment
- 840
- Locations
- 79
- Primary Endpoint
- Stage 1: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR)
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Stage 2 (Arm 1): Livmoniplimab (Dose Optimized)
Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Carboplatin
Stage 2 (Arm 2): Placebo
Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Cisplatin
Stage 1 (Cohort 1): Livmoniplimab Dose A
Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Livmoniplimab
Stage 1 (Cohort 1): Livmoniplimab Dose A
Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Budigalimab
Stage 1 (Cohort 1): Livmoniplimab Dose A
Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Pemetrexed
Stage 1 (Cohort 1): Livmoniplimab Dose A
Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Cisplatin
Stage 1 (Cohort 1): Livmoniplimab Dose A
Participants will receive livmoniplimab (dose A)+ budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Carboplatin
Stage 1 (Cohort 2): Livmoniplimab Dose B
Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Livmoniplimab
Stage 1 (Cohort 2): Livmoniplimab Dose B
Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Budigalimab
Stage 1 (Cohort 2): Livmoniplimab Dose B
Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Pemetrexed
Stage 1 (Cohort 2): Livmoniplimab Dose B
Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Cisplatin
Stage 1 (Cohort 2): Livmoniplimab Dose B
Participants will receive livmoniplimab (dose B) + budigalimab, + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Carboplatin
Stage 1 (Cohort 3): Budigalimab
Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.
Intervention: Budigalimab
Stage 1 (Cohort 3): Budigalimab
Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.
Intervention: Pemetrexed
Stage 1 (Cohort 3): Budigalimab
Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.
Intervention: Cisplatin
Stage 1 (Cohort 3): Budigalimab
Participants will receive budigalimab + chemotherapy for 4 cycles followed by budigalimab + pemetrexed.
Intervention: Carboplatin
Stage 1 (Cohort 4): Pembrolizumab
Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Pembrolizumab
Stage 1 (Cohort 4): Pembrolizumab
Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Pemetrexed
Stage 1 (Cohort 4): Pembrolizumab
Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Cisplatin
Stage 1 (Cohort 4): Pembrolizumab
Participants will receive pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Carboplatin
Stage 2 (Arm 1): Livmoniplimab (Dose Optimized)
Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Livmoniplimab
Stage 2 (Arm 1): Livmoniplimab (Dose Optimized)
Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Budigalimab
Stage 2 (Arm 1): Livmoniplimab (Dose Optimized)
Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Pemetrexed
Stage 2 (Arm 1): Livmoniplimab (Dose Optimized)
Participants will receive livmoniplimab (dose optimized) + budigalimab + chemotherapy for 4 cycles followed by livmoniplimab + budigalimab + pemetrexed.
Intervention: Cisplatin
Stage 2 (Arm 2): Placebo
Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Pembrolizumab
Stage 2 (Arm 2): Placebo
Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Pemetrexed
Stage 2 (Arm 2): Placebo
Participants will receive placebo + pembrolizumab + chemotherapy for 4 cycles followed by pembrolizumab + pemetrexed.
Intervention: Carboplatin
Outcomes
Primary Outcomes
Stage 1: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR)
Time Frame: 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)
Time Frame: Up to 55 Months
OS is defined as the time measured from randomization until death from any cause.
Secondary Outcomes
- Stage 2: PFS per Investigator(Up to 55 Months)
- Stage 1: Progression Free Survival (PFS)(Up to 21 Months)
- Stage 1: Duration of Response (DOR)(Up to 21 Months)
- Stage 1: OS(Up to 21 Months)
- Stage 2: PFS(Up to 55 Months)
- Stage 2: BOR of CR/PR(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)(Up to 55 Months)
- Stage 2: DOR per investigator(Up to 55 Months)
- Stage 2: Change from Baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)(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(Up to 55 Months)
- Stage 1: BOR of CR/PR per Investigator(Up to 21 Months)
- Stage 2: DOR(Up to 55 Months)