Pancreatic Cancer
Conditions
Brief summary
To compare the efficacy of pegilodecakin in combination with FOLFOX versus FOLFOX alone in participants with metastatic pancreatic cancer as measured by overall survival.
Detailed description
This is an open-label, multi-center, randomized, Phase 3 study designed to compare the efficacy and safety of pegilodecakin in combination with FOLFOX versus FOLFOX alone in participants with metastatic adenocarcinoma of the pancreas who have progressed on one prior gemcitabine containing regimen.
Interventions
BIOLOGICALPegilodecakin
Pegilodecakin plus FOLFOX
DRUGFOLFOX
FOLFOX 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. The presence of metastatic pancreatic adenocarcinoma 2. Measurable disease per RECIST v.1.1 3. Participant must have documented tumor progression during or following a gemcitabine containing regimen to treat metastatic disease as established by CT or MRI scan 4. Eastern Cooperative Oncology Group Performance Status of 0 - 1 5. Participant must have completed prior chemotherapy at least 2 weeks (washout period) prior to randomization and recovered from toxicity to Grade 1 or baseline 6. Participants must not have received previous radiation therapy or investigational therapy for the treatment of advanced metastatic disease. 7. Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study 8. No peripheral neuropathy 9. No known history of dihydropyrimidine dehydrogenase deficiency
Exclusion criteria
1. Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non- adenocarcinoma (i.e., lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma 2. Participant on Coumadin and not willing to change to LMWH or oral Factor II or Xa inhibitor with half-life of less than 24 hours. 3. Participant has received prior treatment with pegilodecakin or fluoropyrimidine/platinum containing regimen 4. Participants who were intolerant of a gemcitabine containing regimen. 5. History of positivity for human immunodeficiency virus 6. Chronic active or active viral hepatitis A, B, or C infection 7. Clinically significant bleeding within two weeks prior to randomization (e.g., gastrointestinal (GI) bleeding, intracranial hemorrhage) 8. Pregnant or lactating women 9. Participants with a history of immune-mediated neurological disorders such as multiple sclerosis, Guillain-Barré or inflammatory CNS/PNS disorders 10. Clinically significant ascites defined as requiring ≥ 1 paracentesis every 2- weeks 11. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy),within 28 days prior to randomization or anticipated surgery during the study period 12. Prior history of receiving immune modulators including, but not limited to, anti-CTLA4, anti-PD1, anti-PD-L1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Randomization to date of death from any cause (Up To 30 Months) | Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months) | PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was 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. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant. |
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator | Randomization to PD (Up To 30 Months) | ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response. |
| Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR) | Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up To 30 Months) | Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was 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 (DOR) | Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months) | DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was 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. |
| Percentage of Participants Alive at 1 Year (12-Month Survival Rate) | From randomization to until the date of first documented date of death from any cause within 12 months | The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pegilodecakin + FOLFOX Pegilodecakin 5 μg/kg dosed as one of the following 2 fixed doses: 0.4 mg for participants weighing ≤80 kg or 0.8 mg for participants weighing\>80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX \[dl-Leucovorin (dl-LV) 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2\] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression \[that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity\], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing\>80 kg. | 283 |
| FOLFOX FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5- FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. | 284 |
| Total | 567 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Sponsor Decision | 39 | 38 |
| Overall Study | Unknown, Not Collected | 7 | 6 |
| Overall Study | Withdrawal by Subject | 6 | 13 |
Baseline characteristics
| Characteristic | Pegilodecakin + FOLFOX | Total | FOLFOX |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 9 | 64.0 years STANDARD_DEVIATION 9.4 | 64.1 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 15 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 263 Participants | 528 Participants | 265 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 24 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 59 Participants | 114 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 16 Participants | 8 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) White | 207 Participants | 420 Participants | 213 Participants |
| Region of Enrollment Australia | 14 Participants | 30 Participants | 16 Participants |
| Region of Enrollment Austria | 3 Participants | 13 Participants | 10 Participants |
| Region of Enrollment Belgium | 17 Participants | 36 Participants | 19 Participants |
| Region of Enrollment Canada | 2 Participants | 9 Participants | 7 Participants |
| Region of Enrollment France | 9 Participants | 11 Participants | 2 Participants |
| Region of Enrollment Germany | 9 Participants | 20 Participants | 11 Participants |
| Region of Enrollment Italy | 28 Participants | 67 Participants | 39 Participants |
| Region of Enrollment Poland | 8 Participants | 13 Participants | 5 Participants |
| Region of Enrollment South Korea | 48 Participants | 89 Participants | 41 Participants |
| Region of Enrollment Spain | 42 Participants | 73 Participants | 31 Participants |
| Region of Enrollment Taiwan | 5 Participants | 15 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment United States | 93 Participants | 182 Participants | 89 Participants |
| Sex: Female, Male Female | 135 Participants | 267 Participants | 132 Participants |
| Sex: Female, Male Male | 148 Participants | 300 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 217 / 278 | 188 / 251 |
| other Total, other adverse events | 271 / 278 | 240 / 251 |
| serious Total, serious adverse events | 123 / 278 | 95 / 251 |
Outcome results
Primary
Overall Survival
Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date.
Time frame: Randomization to date of death from any cause (Up To 30 Months)
Population: All randomized participants. The number of participants censored were Pegilodecakin + FOLFOX = 63 and FOLFOX = 73.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + FOLFOX | Overall Survival | 5.78 Months |
| FOLFOX | Overall Survival | 6.28 Months |
Comparison: The primary test to compare overall survival between treatment arms was the two-sided log-rank test, stratified by region and prior therapy. The estimate of the hazard ration (HR) - (Pegilodecakin + FOLFOX Arm / FOLFOX Arm) and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in interactive voice response system (IVRS).p-value: 0.656595% CI: [0.863, 1.265]Log Rank
Secondary
Duration of Response (DOR)
DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was 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: Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months)
Population: All randomized participants who achieved an objective response of CR or PR. The number of participants censored were Pegilodecakin + FOLFOX = 4 and FOLFOX = 7.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + FOLFOX | Duration of Response (DOR) | 4.99 Months |
| FOLFOX | Duration of Response (DOR) | 5.17 Months |
Comparison: The estimate of hazard ratio (HR) was stratified by region and prior therapy.p-value: 0.995295% CI: [0.37, 2.741]Log Rank
Secondary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response.
Time frame: Randomization to PD (Up To 30 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegilodecakin + FOLFOX | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator | 4.6 Percentage of participants |
| FOLFOX | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator | 5.6 Percentage of participants |
p-value: 0.704495% CI: [0.4, 1.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Alive at 1 Year (12-Month Survival Rate)
The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization.
Time frame: From randomization to until the date of first documented date of death from any cause within 12 months
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegilodecakin + FOLFOX | Percentage of Participants Alive at 1 Year (12-Month Survival Rate) | 14.7 Percentage of participants |
| FOLFOX | Percentage of Participants Alive at 1 Year (12-Month Survival Rate) | 19.1 Percentage of participants |
p-value: 0.229895% CI: [-11.6, 2.8]Log Rank
Secondary
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was 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: Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up To 30 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegilodecakin + FOLFOX | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR) | 42.8 Percentage of participants |
| FOLFOX | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR) | 36.6 Percentage of participants |
p-value: 0.146395% CI: [0.9, 1.8]Cochran-Mantel-Haenszel
Secondary
Progression Free Survival
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was 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. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant.
Time frame: Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months)
Population: All randomized participants. The number of participants censored were Pegilodecakin + FOLFOX = 45 and FOLFOX = 86.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pegilodecakin + FOLFOX | Progression Free Survival | 2.14 Months |
| FOLFOX | Progression Free Survival | 2.10 Months |
Comparison: The estimate of hazard ratio (HR) was stratified by region and prior therapy.p-value: 0.814495% CI: [0.808, 1.19]Log Rank