Non Small Cell Lung Cancer
Conditions
Brief summary
To compare the efficacy of pegilodecakin in combination with nivolumab versus nivolumab alone in participants with metastatic non-small cell lung cancer as measured by objective response rate.
Detailed description
This is an open-label, multi-center, randomized, Phase 2 study designed to compare the efficacy and safety of pegilodecakin in combination with nivolumab versus nivolumab alone in participants with stage IV / metastatic wild type non-small cell lung cancer and tumors with low tumor expression of PD-L1 (0-49%).
Interventions
BIOLOGICALPegilodecakin
Pegilodecakin plus Nivolumab
DRUGNivolumab
Nivolumab Alone
Sponsors
ARMO BioSciences
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must have histologically or cytologically confirmed Wild Type NSCLC that is stage IV / metastatic or recurrent 2. Participants must have received at least one prior systemic therapy that was not an anti-PD-1, anti-PD-L1 and/or anti-CTLA-4 treatment for the advanced stage of the disease 3. Participants with tumor tissue low expression of PD-L1 as defined by Tumor Proportion Score (TPS) 0% - 49% 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Participants with measurable disease by spiral computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1 criteria 6. Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization
Exclusion criteria
1. Participants with active central nervous system (CNS) metastases or carcinomatous meningitis 2. Participants with any serious or uncontrolled medical disorder or active infection with the hepatitis virus or the human immunodeficiency virus (HIV) 3. Participants with Grade 1 (NCI-CTCAE v.4.03) toxicities attributed to prior anti-cancer therapy (other than alopecia and fatigue) prior to randomization 4. Participants that have received nivolumab 5. Participants that have received therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents 6. Participants with a history of severe hypersensitivity reactions to monoclonal antibodies 7. Participants that have received therapy with anti-PD-1, anti-PD-L1, anti-PD-L-2, anti-CD-137, and/or anti CTLA-4 antibodies 8. Participants receiving any investigational agent within 28 days of first administration of trial treatment 9. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized) | Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized) | OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive. |
| Progression Free Survival (PFS) | From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized) | PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment. |
| Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization) | Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
| Duration of Response | From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized) | Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment. |
Countries
United States
Participant flow
Pre-assignment details
Completer's included participants who had progression free survival events (Progressive Disease (PD) or death).
Participants by arm
| Arm | Count |
|---|---|
| Pegilodecakin + Nivolumab Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm.
Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W, or 480 mg Q4W. | 27 |
| Nivolumab Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W, or 480 mg Q4W. | 25 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor Decision | 6 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 5 |
Baseline characteristics
| Characteristic | Pegilodecakin + Nivolumab | Total | Nivolumab |
|---|---|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 8.2 | 67.2 years STANDARD_DEVIATION 9.3 | 65.9 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 44 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 23 Participants | 43 Participants | 20 Participants |
| Region of Enrollment United States | 27 Participants | 52 Participants | 25 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 17 Participants | 31 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 27 | 12 / 24 |
| other Total, other adverse events | 27 / 27 | 22 / 24 |
| serious Total, serious adverse events | 13 / 27 | 9 / 24 |
Outcome results
Primary
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time frame: From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegilodecakin + Nivolumab | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 14.8 Percentage of participants |
| Nivolumab | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 12.0 Percentage of participants |
95% CI: [0.3, 5.9]
Secondary
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegilodecakin + Nivolumab | Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | 37.0 Percentage of participants |
| Nivolumab | Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | 28.0 Percentage of participants |
95% CI: [0.4, 4.1]
Secondary
Duration of Response
Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.
Time frame: From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)
Population: All randomized participants who received at least one dose of study drug and had CR or PR responses. Participants censored: Pegilodecakin + Nivolumab = 3 and Nivolumab = 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + Nivolumab | Duration of Response | NA Months |
| Nivolumab | Duration of Response | 3.06 Months |
Secondary
Overall Survival (OS)
OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive.
Time frame: From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)
Population: All randomized participants. Participants censored: Pegilodecakin + Nivolumab = 6 and Nivolumab = 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + Nivolumab | Overall Survival (OS) | 1.87 Months |
| Nivolumab | Overall Survival (OS) | 1.94 Months |
95% CI: [0.519, 1.951]
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.
Time frame: From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized)
Population: All randomized participants. Participants censored: Pegilodecakin + Nivolumab = 12 and Nivolumab = 16.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + Nivolumab | Progression Free Survival (PFS) | 6.70 Months |
| Nivolumab | Progression Free Survival (PFS) | 10.74 Months |
95% CI: [0.772, 4.532]