A Phase 1B Study of Canakinumab, Spartalizumab, Nab-paclitaxel, and Gemcitabine in Metastatic Pancreatic Cancer (PC) Patients

NCT04581343 | Completed Phase 1 Results FDA Drug

• 1 other identifier: PanCAN-SR1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study combines canakinumab (ACZ885), a high-affinity human anti-interleukin-1β (IL-1β) monoclonal antibody (mAb), and spartalizumab (PDR001), a mAb directed against human Programmed Death-1 (PD-1), with the chemotherapy combination of gemcitabine and nab-paclitaxel. This study will confirm for this 4-drug combination the tolerable doses, the acceptable safety profile, and the dose to be used for a Phase II combination treatment regimen.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• The Incidence of DLTs in the First 56 Days (8 Weeks) of Dosing to Determine Tolerable Phase 2/3 Dose of Canakinumab, Spartalizumab, Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer.

  Evaluate dose limiting toxicities of patients with metastatic pancreatic cancer for at least 56 days (DLT period) after dosing with canakinumab at 250 mg every 4 weeks (Q4W), 400mg Spartalizumab Q4W and Gemcitabine/nab-paclitaxel on Days 1, 8 and 15 at standard of care levels. Dose limiting toxicities were evaluated to determine if dosing of canakinumab at 250 mg every 4 weeks with the other three drugs was considered tolerable and should be the dose utilized for future Phase 2/3 clinical trials. The starting dose level of canakinumab explored was 250 mg every 4 weeks (Q4W) ("starting dose level"). In case of unacceptable toxicity of canakinumab at 250 mg Q4W, the dose of canakinumab was to be de-escalated to 250 mg every 8 weeks, while other components of the combination were kept at the same dose as the starting dose level. Approximately 10 patients were to be enrolled in this study to have at least 6 evaluable patients per dose level of canakinumab.

  Assess the incidence of dose limiting toxicities (DLT) in the first 56 days (8 weeks) of dosing

Secondary Outcomes (11)

• To Determine the Safety and Tolerability of Canakinumab in Combination With Spartalizumab, Nab-paclitaxel, and Gemcitabine

  From Day 1 of study treatment through Safety Follow-up period (150-days after the last study treatment)

• Determine the Tolerability of Canakinumab, Spartalizumab, Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

  From Day 1 of study treatment through End of Treatment visit, an average of 6 months

• Determine the Response-related Efficacy Assessments Objective Response Rate (ORR) and Duration of Response (DOR) of Canakinumab, Spartalizumab, Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

  Tumor response data from CT/MRI scans will be taken at screening visit and every 8 weeks throughout study treatment, an average of 6 months;

• Determine the Disease Control Rate (DCR) of Canakinumab, Spartalizumab, Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

  Tumor response data from CT/MRI scans will be taken at screening visit and every 8 weeks throughout study treatment, an average of 6 months;

• Determine the Progression Free Survival (PFS) of Canakinumab, Spartalizumab, Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

  Tumor response data from CT/MRI scans will be taken at screening visit and every 8 weeks throughout study treatment, an average of 6 months;

Other Outcomes (12)

• Study the Immunogenicity [by Tabulating the Anti-drug Antibodies (ADA) Prevalence at Baseline and ADA Incidence On-treatment] of Canakinumab, and Spartalizumab Combined With Nab-paclitaxel and Gemcitabine in Metastatic Pancreatic Cancer Patients

  Immunogenicity Samples of canakinumab analytes are taken during Cycles 1-6 of study treatment; Every cycle is 28-days, total estimated time is 6 months;

• Study the Immunogenicity [by Tabulating the Anti-drug Antibodies (ADA) Prevalence at Baseline and ADA Incidence On-treatment] of Canakinumab, and Spartalizumab Combined With Nab-paclitaxel and Gemcitabine in Metastatic Pancreatic Cancer Patients

  Immunogenicity Samples of spartalizumab analytes are taken during Cycles 1-6 of study treatment; Every cycle is 28-days, total estimated time is 6 months;

• Study the Immune Modulation Effect of This 4-drug Combination on the Tumor Micro-environment Using Sample Analysis From Tissue Biopsies.

  Tissue samples will be taken at two timepoints: at baseline visit (Prior to treatment) and after 8-weeks of study treatment;

Study Arms (1)

Canakinumab, spartalizumab, nab-paclitaxel and gemcitabine

EXPERIMENTAL

Spartalizumab (PDR001),IV infusion, 400 mg, D1 of each 28-day cycle; Canakinumab (ACZ885), s.c. injection, 250 mg, Day 1 of each 28- day cycle; Gemcitabine, IV Infusion, 1000 mg/m2, Days 1, 8, 15 of each 28-day cycle; Nab-paclitaxel, IV Infusion, 125 mg/m2, Days 1, 8, 15 of each 28-day cycle.

Drug: Canakinumab injection; spartalizumab, nab-paclitaxel, gemcitabine

Interventions

Canakinumab injection; spartalizumab, nab-paclitaxel, gemcitabine DRUG

Canakinumab 250 mg s.c. injection; Spartalizumab 400 mg IV infusion, nab-paclitaxel 125 mg/m2 IV infusion, gemcitabine 1000 mg/m2 IV infusion

Also known as: Ilaris, Abraxane

Canakinumab, spartalizumab, nab-paclitaxel and gemcitabine

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years at the time of informed consent
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) (determined by a local laboratory) with metastatic spread of disease (adenosquamous is also allowed).
• Patients must have not received previous anti-cancer therapy for the treatment of metastatic pancreatic ductal adenocarcinoma.
• Patients who received previous neo-/adjuvant systemic therapy for non-metastatic PDAC ≥12 months from the last treatment to study enrollment date are allowed unless this therapy included immunotherapy and/or IL-1 inhibitors.
• Radiographically measurable disease of at least one site by computed tomography (CT) scan (or magnetic resonance imaging, if allergic to CT contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Primary lesion is allowed as long as it is measurable (per RECIST 1.1) and has not been previously irradiated. Imaging results must be obtained within the 28-day screening window.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function (laboratory results must be obtained within the 28-day screening window)
• Absolute neutrophil count \> 1500/mm3
• Hemoglobin \> 9 g/dL
• Platelets \> 100,000/mm3
• Serum creatinine \< 1.5 x upper limit normal (ULN), or calculated creatinine clearance \> 60 mL/min (Cockcroft Gault)
• Albumin \> 3.0 g/dL
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) \< 3.0 x ULN (\< 5 x ULN in presence of liver metastasis).
• In patients with elevated ALT or AST, the values must be stable for at least 2 weeks and with no evidence of biliary obstruction on imaging
• Total bilirubin ≤ 1.5 X ULN

You may not qualify if:

• Diagnosis of pancreatic neuroendocrine carcinoma or pancreatic acinar cell carcinoma
• Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways).
• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer
• Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1 inhibitor).
• History of known hypersensitivity to any of the drugs used in this study or any of their excipients, or patient has contraindication to any of the study drugs as outlined in the local prescribing information (e.g. United States Prescribing Information \[USPI\])
• Active autoimmune disease that has required systemic treatment in the past 2 years prior to enrollment i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs. Control of the disorder with replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
• Patient with suspected or proven immunocompromised state or infections, including:
• Evidence of active or latent tuberculosis (TB) as determined by locally approved screening methods. If the results of the screening per local treatment guidelines or clinical practice require treatment, then the patient is not eligible.
• Chronic or active hepatitis B or C
• Known history of testing positive for Human Immunodeficiency Virus (HIV) infections.
• Any other medical condition (such as active infection, treated or untreated), which in the opinion of the investigator places the patient at an unacceptable risk for participation in immunomodulatory therapy.
• Note: Patients with localized condition unlikely to lead to a systemic infection e.g. chronic nail fungal infection are eligible.
• Allogeneic bone marrow or solid organ transplant
• Treatment with any immune modulating agent in doses with systemic effects e.g.:
• Systemic treatment with prednisone \> 10 mg (or equivalent) for \>14 days within 4 weeks prior to the first dose of study treatment.

Sponsors & Collaborators

• Pancreatic Cancer Action Network: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

New York University

New York, New York, 10016, United States

Location

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MeSH Terms

Interventions

canakinumab; spartalizumab; 130-nm albumin-bound paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Samantha Pedersen, Sr. Director Clinical Operations
• Organization: PanCAN

spedersen@pancan.org

310.706.3726

Study Officials

• Anna Berkenbilt

  Pancreatic Cancer Action Network

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Phase 1B study enrolling 10 patients to find 6 evaluable patients starting at a maximum dose. If Dose Limiting Toxicities are noted a lower dose may be evaluated to determine the recommended Phase II dose level.

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: October 9, 2020
• Study Start: November 2, 2020
• Primary Completion: November 2, 2022
• Study Completion: February 27, 2023
• Last Updated: May 4, 2025
• Results First Posted: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)