Breast Cancer, Colorectal Carcinoma, Melanoma, Non-small Cell Lung Carcinoma, Ovarian Cancer, Pancreatic Carcinoma, Prostate Cancer, Renal Cell Carcinoma, Solid Tumors
Conditions
Keywords
Phase 1/Phase 1b, Oncology, Cancer, Solid Tumors
Brief summary
This is a first-in-human, open-label, dose escalation study to evaluate the safety and tolerability of pegilodecakin in participants with advanced solid tumors, dosed daily subcutaneously as a monotherapy or in combination with chemotherapy or immunotherapy.
Interventions
DRUGPegilodecakin
Daily subcutaneous injections of pegilodecakin up to 12 months
DRUGPaclitaxel or Docetaxel and Carboplatin or Cisplatin
Platinum/ Taxane administered IV on Day 1 of every 21 day cycle
FOLFOX administered IV on Day 1 and 2 of every 14 day cycle
Gemcitabine/nab-paclitaxel administered IV on Day 1, 8 and 15 of each 28 day treatment cycle.
DRUGCapecitabine
Capecitabine administered orally twice daily for 14 days out of every 21 days.
DRUGPazopanib
Pazopanib administered orally daily continuously
DRUGPembrolizumab
Pembrolizumab administered IV on Day 1 of every 21 day cycle.
DRUGPaclitaxel
Paclitaxel administered IV on Days 1, 8, 15 of each cycle (28 days= 1 cycle)
DRUGnivolumab
Nivolumab administered IV on Day 1 of each cycle (14 days = 1 cycle)
Gemcitabine and carboplatin administered IV on Days 1, 8 of each cycle (21 days = 1 cycle)
Sponsors
Eli Lilly and Company
ARMO BioSciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A Escalation Cohorts: o Histologically or cytologically confirmed advanced malignant solid tumor, limited to melanoma, castrate resistant prostate cancer (CRPC), ovarian cancer (OVCA), renal cell carcinoma, colorectal carcinoma (CRC), pancreatic carcinoma or non-small cell lung carcinoma (NSCLC) that is refractory to, intolerant of, for which no standard of therapy is available or where the participant refuses existing therapies Part A Expansion Cohorts, Part B and C Escalation and Expansion Cohorts: * Tumors with all histological diagnosis or tissue origin may be enrolled * Participants must have failed prior standard curative chemotherapy for their disease, refuse existing therapies OR the proposed chemotherapy regimen to which pegilodecakin is added represents an acceptable standard treatment for their disease. * Measurable or evaluable disease according to irRC or bone metastatic disease evaluable by Prostate Cancer Working Group 2 criteria (PCWG2) for castration-resistant prostate cancer (CRPC) * At least 18 years of age * Performance Status of 0 or 1 * Adequate organ function
Exclusion criteria
* Hematologic malignancies * Pregnant or lactating * Present or history of neurological disorders such as Multiple Sclerosis and Guillain Barre or inflammatory central nervous system/peripheral nervous system (CNS/PNS) disorders * Myocardial infarction within the last 6 months * Unstable angina, or unstable cardiac arrhythmia requiring medication * Surgery within the last 28 days * Systemic fungal, bacterial, viral, or other infection * History of bleeding diathesis within the last 6 months * Positive for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs and SAEs Observed During the Study of Pegilodecakin | From first dose of study drug through 30 days after the last dose of study drug (Up to 63 Months) | The number of participants who experienced treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the study. |
| Pharmacokinetic (PK): Serum Concentration of Pegilodecakin | Day 29 | Serum concentration of Pegilodecakin is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-Pegilodecakin Antibody Formation | Up to 63 Months | Number of participants with treatment-emergent anti-Pegilodecakin antibodies, defined as participants with at least one postbaseline anti-drug antibody (ADA) titer ≥4-fold increase from baseline (treatment-boosted) or ADA present with titer ≥1:20 if baseline ADA was negative (treatment-induced), analyses were conducted in the TE ADA-evaluable population. A participant is TE ADA evaluable if at least one non-missing ADA result is available at both baseline and postbaseline. |
| Part A: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of study drug until Disease Progression or Death (Up to 54 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR). irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part B: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 11 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part C: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study drug until Disease Progression or Death (Upto 23 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part D: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 7 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part E: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of study drug until Disease Progression or Death (Upto 12 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part F: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 3 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part G: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 11 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part H: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 48 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part I: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 50 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
| Part J: Number of Participants With Overall Response Rate (ORR) | From Date of First Dose of Study Drug until Disease Progression or Death (Up to 8 months) | Overall response rate was assessed according to Immune-related Response Criteria (irRC) (Wolchok, Hoos et al. 2009). ORR is the number of participants with a best overall response of irCR or irPR. irCR is defined as complete disappearance of all lesions with no new lesions; irPR as a ≥50% decrease in tumor burden from baseline; both are confirmed ≥4 weeks after initial documentation. Only participants with adequate irRC tumor assessments (baseline and ≥1 post-baseline) and without major protocol deviations, were included in the analysis. |
Countries
United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 138 Participants |
| Age, Categorical Between 18 and 65 years | 215 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 291 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 6 / 6 | 6 / 6 | 6 / 6 | 105 / 117 | 5 / 5 | 4 / 4 | 3 / 3 | 14 / 18 | 4 / 4 | 27 / 29 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 4 / 6 | 8 / 14 | 29 / 34 | 3 / 5 | 0 / 1 | 33 / 57 | 5 / 5 | 5 / 5 |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 6 / 6 | 6 / 6 | 116 / 117 | 5 / 5 | 4 / 4 | 3 / 3 | 18 / 18 | 4 / 4 | 29 / 29 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 14 / 14 | 34 / 34 | 5 / 5 | 1 / 1 | 56 / 57 | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 3 / 4 | 2 / 6 | 2 / 6 | 2 / 6 | 60 / 117 | 2 / 5 | 0 / 4 | 1 / 3 | 10 / 18 | 3 / 4 | 14 / 29 | 3 / 6 | 2 / 6 | 4 / 6 | 4 / 6 | 1 / 6 | 8 / 14 | 16 / 34 | 3 / 5 | 1 / 1 | 32 / 57 | 2 / 5 | 1 / 5 |
Outcome results
None listed