A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors

• Pegilodecakin (Drug), also known as LY3500518, AM0010, PEGylated recombinant human Interleukin-10, PEG-rHuIL-10: Daily subcutaneous injections of pegilodecakin up to 12 months
• Paclitaxel or Docetaxel and Carboplatin or Cisplatin (Drug), also known as Taxol or taxotere and paraplatin or platinol: Platinum/ Taxane administered IV on Day 1 of every 21 day cycle
• FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) (Drug), also known as Eloxatin®/Leucovorin/5-FU: FOLFOX administered IV on Day 1 and 2 of every 14 day cycle
• gemcitabine/nab-paclitaxel (Drug), also known as Gemzar/Abraxane ABI-007: Gemcitabine/nab-paclitaxel administered IV on Day 1, 8 and 15 of each 28 day treatment cycle.
• Capecitabine (Drug), also known as Xeloda: Capecitabine administered orally twice daily for 14 days out of every 21 days.
• Pazopanib (Drug), also known as GW786034: Pazopanib administered orally daily continuously
• Pembrolizumab (Drug), also known as Keytruda, MK-3475: Pembrolizumab administered IV on Day 1 of every 21 day cycle.
• Paclitaxel (Drug): Paclitaxel administered IV on Days 1, 8, 15 of each cycle (28 days= 1 cycle)
• nivolumab (Drug), also known as Opdivo: Nivolumab administered IV on Day 1 of each cycle (14 days = 1 cycle)
• Gemcitabine/carboplatin (Drug), also known as gemzar/paraplatin: Gemcitabine and carboplatin administered IV on Days 1, 8 of each cycle (21 days = 1 cycle)

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to any

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

• Results publication: Naing A, Wong DJ, Infante JR, Korn WM, Aljumaily R, Papadopoulos KP, Autio KA, Pant S, Bauer TM, Drakaki A, Daver NG, Hung A, Ratti N, McCauley S, Van Vlasselaer P, Verma R, Ferry D, Oft M, Diab A, Garon EB, Tannir NM. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol. 2019 Nov;20(11):1544-1555. doi: 10.1016/S1470-2045(19)30514-5. Epub 2019 Sep 25. PMID 31563517
• Results publication: Naing A, Papadopoulos KP, Autio KA, Ott PA, Patel MR, Wong DJ, Falchook GS, Pant S, Whiteside M, Rasco DR, Mumm JB, Chan IH, Bendell JC, Bauer TM, Colen RR, Hong DS, Van Vlasselaer P, Tannir NM, Oft M, Infante JR. Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors. J Clin Oncol. 2016 Oct 10;34(29):3562-3569. doi: 10.1200/JCO.2016.68.1106. PMID 27528724

• Study Protocol (PDF, 2019-02-25)
• Statistical Analysis Plan (PDF, 2019-05-09)

• Call 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), Study director, Eli Lilly and Company