Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer

NCT04191421 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB00105616NCI-2018-01793Winship4463-18P30CA138292
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief Summary

This phase Ib/II trial studies the best dose and side effects of siltuximab and how well it works in combination with spartalizumab in treating patients with pancreatic cancer that has spread to other places in the body. Monoclonal antibodies, such as siltuximab and spartalizumab, interfere with the ability of tumors cells to grow and spread.

Conditions

Metastatic Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Maximal Tolerated Dose (MTD) of Siltuximab That Can be Combined With Spartalizumab

  Maximal tolerated dose (MTD )is defined as the dose at which less than one-third of the subjects experience a dose-limiting toxicity (DLT) in the first 6 weeks of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as definitely at least possibly related to study treatment treatment related that occurs within the first 6 weeks. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

  Up to 6 weeks from study start

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 2 years from study start

• Response Duration

  From treatment start until progression or death, assessed up to 2 years

• Progression-free Survival

  From treatment start until progression or death, assessed up to 2 years

• Overall Survival Time

  From treatment start until progression or death, assessed up to 2 years

Study Arms (4)

Treatment spartalizumab and siltuximab Phase I dose level 1

EXPERIMENTAL

Arm 1 (Phase I dose level 1) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 6 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Siltuximab; Biological: Spartalizumab

Treatment spartalizumab and siltuximab Phase I level 2

EXPERIMENTAL

Arm 2 (Phase I dose level 2) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 11 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Siltuximab; Biological: Spartalizumab

Treatment spartalizumab and siltuximab phase I level 2a

EXPERIMENTAL

Arm 3 (Phase I dose level 2a) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab 9 mg/Kg IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Siltuximab; Biological: Spartalizumab

Treatment spartalizumab and siltuximab phase II

EXPERIMENTAL

Arm 4 (Phase II ) Participants receive spartalizumab 300 mg IV over 30 minutes on day 1 and siltuximab at dose determined in Arm 1 to 3 IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Siltuximab; Biological: Spartalizumab

Interventions

Siltuximab BIOLOGICAL

Given IV

Also known as: Anti-IL-6 Chimeric Monoclonal Antibody, cCLB8, CNTO 328, Sylvant

Treatment spartalizumab and siltuximab Phase I dose level 1; Treatment spartalizumab and siltuximab Phase I level 2; Treatment spartalizumab and siltuximab phase I level 2a; Treatment spartalizumab and siltuximab phase II

Spartalizumab BIOLOGICAL

Given IV

Also known as: PDR001

Treatment spartalizumab and siltuximab Phase I dose level 1; Treatment spartalizumab and siltuximab Phase I level 2; Treatment spartalizumab and siltuximab phase I level 2a; Treatment spartalizumab and siltuximab phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytological or histologic diagnosis and metastatic pancreatic adenocarcinoma disease that has failed at least one standard regimen such as gemcitabine nab-paclitaxel or folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX).
• Patient must meet the following laboratory values at the screening visit:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelets ≥ 75 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine \< 1.5 mg/dL OR Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula
• Total bilirubin ≤ 1.5 x ULN
• Aspartate transaminase (AST) ≤ 2.5 x ULN, except for patients with liver metastasis, who may only be included if AST ≤ 5.0 x upper limit of normal (ULN)
• Alanine transaminase (ALT) ≤ 2.5 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤ 5.0 x ULN
• Presence of measurable disease by RECIST criteria
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Written informed consent must be obtained prior to any screening procedures.
• Normal ECG defined as the following:
• Resting heart rate 50-90 bpm
• QT corrected for HR using Fridericia's method (QTcF) at screening \< 450 ms (male patients), \< 460 ms (female patients)

You may not qualify if:

• Prior exposure to agents targeting programmed cell death protein-1 (PD-1), PD-L1, IL-6 or the IL-6 receptor. Prior chemotherapy is allowed as long as adequate washout period of ≥ 4 weeks.
• Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥ 2 weeks.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Note: Topical, inhaled, nasal and ophthalmic steroids are allowed.
• Active, known or suspected autoimmune disease or a documented history of autoimmune disease Note: Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted).
• Allogenic bone marrow or solid organ transplant.
• History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
• Known history or current interstitial lung disease or non-infectious pneumonitis.
• Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B surface antigen positivity.
• Clinically significant ongoing infection.
• Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half-lives before enrollment (whichever is longer) or is currently enrolled in the treatment stage of an investigational study.
• A woman who is pregnant or breast-feeding, or a woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 150 days after the last dose of study agent.
• Had hospitalization for infection or major surgery (eg, requiring general anesthesia) within 2 weeks before enrollment or have not fully recovered from surgery. Note: subjects with surgical procedures conducted under local anesthesia may participate.
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within last 6 months)

Sponsors & Collaborators

• Emory University: lead
• Novartis: collaborator
• EUSA Pharma, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

siltuximab; spartalizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Olatunji Alese, MD
• Organization: Emory University

olatunji.alese@emory.edu

404-778-6639

Study Officials

• Olatunji Alese, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Arm 1- (Phase I dose level 1)- Siltuximab 6 mg/Kg every 3 weeks and Spartalizumab 300mg every 3 weeks Arm 2- (Phase I dose level 2)- Siltuximab 11 mg/Kg every 3 weeks and spartalizumab 300 mg every 3weeks Arm 3 - (Phase I doe level 2a)- Siltuximab 9 mg/Kg every 3 weeks and spartalizumab 300 mg every 3weeks Arm 4- (Phase II)- Siltuximab RP2D determined in Arms 1 to 3 and spartalizumab 300 mg every 3weeks

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 9, 2019
• Study Start: January 17, 2020
• Primary Completion: April 5, 2023
• Study Completion: April 5, 2023
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)