Lung Cancer
Conditions
Keywords
Non-small cell lung cancer, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor
Brief summary
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).
Interventions
DRUGNivolumab
Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.
DRUGEpacadostat
Epacadostat administered orally at the protocol-defined dose twice daily.
DRUGPlacebo
Matching placebo for epacadostat administered orally twice daily.
DRUGCarboplatin
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGCisplatin
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGGemcitabine
Gemcitabine administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGPaclitaxel
Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
DRUGPemetrexed
Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if eligible.
Sponsors
Bristol-Myers Squibb
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Approximately 38 months | Defined as the time from randomization to the date of death from any cause. |
| Progression-free Survival (PFS) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Approximately 25 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimate of OS of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Approximately 38 months | Defined as the time from randomization to the date of death from any cause. |
| Estimate of PFS of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Approximately 25 months | 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. |
| Objective Response Rate (ORR) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Approximately 25 months | 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. |
| Estimate of DOR of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Approximately 25 months | 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. |
| Estimate of ORR of Nivolumab and Placebo in Combination With Chemotherapy (Arm C) | Approximately 25 months | 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. |
| Duration of Response (DOR) of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Arm A) Compared to Chemotherapy (Arm B) | Approximately 25 months | 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. |
Countries
United States
Participant flow
Recruitment details
Approximately 630 participants were planned to be randomized. Prior to the termination of the study, 2 participants were randomized to the Platinum Doublet Chemotherapy arm (Arm B) and treated.
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab + Epacadostat/Platinum Doublet Chemotherapy Nivolumab + Epacadostat/Platinum Doublet Chemotherapy included the following:
Nivolumab was administered intravenously at the protocol-defined dose every 3 weeks. Epacadostat was administered orally at the protocol-defined dose twice daily. Carboplatin was administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Cisplatin was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Gemcitabine was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Paclitaxel was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Pemetrexed was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles.
Optional continuation maintenance was available every 3 weeks, if eligible. | 0 |
| Platinum Doublet Chemotherapy Platinum Doublet Chemotherapy included the following:
Carboplatin was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Cisplatin was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Gemcitabine was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Paclitaxel was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Pemetrexed was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles.
Optional continuation maintenance was available every 3 weeks, if eligible. | 2 |
| Nivolumab + Placebo Combination/Platinum Doublet Chemotherapy Nivolumab plus placebo in combination with platinum doublet chemotherapy included:
Nivolumab was administered intravenously at the protocol-defined dose every 3 weeks. : Matching placebo for epacadostat was administered orally twice daily. Carboplatin was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Cisplatin was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Gemcitabine was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Paclitaxel was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles. Pemetrexed was administered intravenously at the protocol-defined dose every 3 weeks up to 4 cycles.
Optional continuation maintenance was available every 3 weeks, if eligible. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reason by the sponsor | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Nivolumab + Epacadostat/Platinum Doublet Chemotherapy | Platinum Doublet Chemotherapy | Nivolumab + Placebo Combination/Platinum Doublet Chemotherapy | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White or Caucasian | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 1 / 2 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 1 / 2 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Approximately 38 months
Population: All randomized participants; Arm A did not enroll any participants in the study and as a result no comparisons were performed and since the study was terminated early no efficacy analyses were conducted.
Primary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm A did not enroll any participants in the study and as a result no comparisons were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm A did not enroll any participants in the study and as a result no comparisons were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm C did not enroll any participants in the study and as a result no analyses were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm C did not enroll any participants in the study and as a result no analyses were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 38 months
Population: All randomized participants; Arm C did not enroll any participants in the study and as a result no analyses were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm C did not enroll any participants in the study and as a result no analyses were performed and since the study was terminated early no efficacy analyses were conducted.
Secondary
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.
Time frame: Approximately 25 months
Population: All randomized participants; Arm A did not enroll any participants in the study and as a result no comparisons were performed and since the study was terminated early no efficacy analyses were conducted.