Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of the combination of nivolumab plus epacadostat in combination with platinum chemotherapy compared with platinum chemotherapy alone, in participants with treatment-naïve Stage 4 or recurrent non-small cell lung cancer (NSCLC).

Official Title
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A Phase 3, Randomized, Global Trial of Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in First-line Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Epacadostat
* Drug: Placebo
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Gemcitabine
* Drug: Paclitaxel
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage IV or recurrent NSCLC of squamous or non-squamous histology that is not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). No prior treatment with systemic anti-cancer therapy for Stage IV disease. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to1. Measurable disease by computed tomography or magnetic resonance imaging per RECIST v1.1. Documentation of program death ligand-1 (PD-L1) status of 0 to 49% by IHC performed by the central laboratory prior to randomization. Other protocol inclusion criteria may apply Exclusion Criteria: Known epidermal growth factor receptor (EGFR) mutations sensitive to available targeted inhibitor therapy. Known ALK or ROS1 rearrangements sensitive to available targeted inhibitor therapy. Untreated central nervous system (CNS) metastases. Unevaluable PD-L1 status or PD-L1 status of ≥ 50% by IHC performed by a central laboratory. Carcinomatous meningitis. Active, known or suspected autoimmune disease. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, IDO1 targeted agent, or any other antibody or drug targeting T cell co-stimulation or checkpoint pathways. History of allergy or hypersensitivity to platinum-containing compounds or study drug components. Physical and laboratory test findings outside the protocol-defined range. Other protocol exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Nivolumab plus epacadostat in combination with platinum doublet | Drug: Nivolumab<br>* Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.<br>* Other names: BMS-936558;Drug: Epacadostat<br>* Epacadostat administered orally at the protocol-defined dose twice daily.<br>* Other names: INCB024360;Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Gemcitabine<br>* Gemcitabine administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if eligible.<br>|
| Active Comparator: Arm B<br>Platinum doublet chemotherapy | Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Gemcitabine<br>* Gemcitabine administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if eligible.<br>|
| Experimental: Arm C<br>Nivolumab plus placebo in combination with platinum doublet chemotherapy. | Drug: Nivolumab<br>* Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.<br>* Other names: BMS-936558;Drug: Placebo<br>* Matching placebo for epacadostat administered orally twice daily.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Gemcitabine<br>* Gemcitabine administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if eligible.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Defined as the time from randomization to the date of death from any cause. | Approximately 38 months | 
| Progression-free Survival (PFS) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Defined as the time between the date of randomization and the first date of documented progression assessed by blinded independent central review, or death due to any cause, whichever occurs first. | Approximately 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Defined as the proportion of participants who achieve a confirmed best response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by blinded independent central review. | Approximately 25 months | 
| Duration of Response (DOR) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Defined as the time between the date of first confirmed response and the date of the first documented tumor progression (per RECIST v1.1) assessed by blinded independent central review or death due to any cause, whichever occurs first. | Approximately 25 months | 
| Estimate of OS of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Defined as the time from randomization to the date of death from any cause. | Approximately 38 months | 
| Estimate of PFS of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Defined as the time between the date of randomization and the first date of documented progression assessed by blinded independent central review or death due to any cause, whichever occurs first. | Approximately 25 months | 
| Estimate of ORR of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Defined as the proportion of participants who achieve a confirmed best response of CR or PR per RECIST v1.1 criteria as assessed by blinded independent central review. | Approximately 25 months | 
| Estimate of DOR of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Defined as the time between the date of first confirmed response and the date of the first documented tumor progression (per RECIST v1.1) assessed by blinded independent central review or death due to any cause, whichever occurs first. | Approximately 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor