A Phase IB Study to Determine the Safety and Tolerability of Canakinumab and Tislelizumab in Combination With Nab-Paclitaxel and Gemcitabine in the Neo-adjuvant Treatment of Patients With Pancreatic Cancer

NCT05984602 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-01205
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this Single Arm Phase Ib clinical trial is to test standard of care chemotherapy and anti PD1 and IL1b to evaluate the safety and preliminary toxicity of this quadruplet regimen prior to resection in patients with pancreatic cancer. The main objectives it aims to answer are to:

• Determine the recommended Phase II dose regimen of canakinumab and tislelizumab in combination with gemcitabine and nab-paclitaxel in patients with localized pancreatic ductal adenocarcinoma.
• Estimate the proportion of patients who proceed to surgical resection.
• Determine the safety and tolerability of canakimumab in combination with tislelizumab, nab-paclitaxel and gemcitabine
• Assess the preliminary clinical anti-tumor activity of canakimumab in combination with tislelizumab, nab-paclitaxel and gemcitabine
• Assess whether therapy has any impact on surgical options Participants will have labs drawn, CT scans, and a treatment administered consisting of:
• Gemcitabine
• Nab-paclitaxel
• Canakinumab
• Tislelizumab

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer, GI cancer

Outcome Measures

Primary Outcomes (2)

• Number of dose limiting toxicities (DLTs)

  A dose-limiting toxicity (DLT) is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 8 weeks of study treatment. NCI CTCAE v5.0 will be used for all grading.

  56 days

• Number of patients who proceeded to surgical resection

  The study team will collaborate with the surgical team to review whether there are any delays or change in outcome in surgery that is attributed to study drug.

  End of treatment (up to 6 months)

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 6 months post treatment

• R0 resection rate (R0)

  At surgery post treatment (up until 6 months)

• Progression Free Survival (PFS)

  Up to 6 months after patients last treatment

• Overall Survival (OS)

  Up to 6 months after patients last treatment

• Number of delays outcome of surgery that is attributed to study drug

  At surgery post treatment (up until 6 months)

Study Arms (1)

Quadruplet regimen prior to resection for pancreatic cancer

EXPERIMENTAL

Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)

Drug: Canakinumab; Drug: Tislelizumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine

Interventions

Canakinumab DRUG

250 mg subcutaneous injection in prefilled syringes on day 1 of every 28-day cycle

Also known as: ACZ885

Quadruplet regimen prior to resection for pancreatic cancer

Tislelizumab DRUG

300 mg in a liquid vial (concentrate for intravenous (i.v.) solution) on day 1 of every 28-day cycle

Quadruplet regimen prior to resection for pancreatic cancer

Nab-Paclitaxel DRUG

125 mg/m2 intravenous infusion on days 1, 8, 15 of every 28-day cycle

Quadruplet regimen prior to resection for pancreatic cancer

Gemcitabine DRUG

1000 mg/m2 intravenous infusion on days 1, 8, 15 of every 28-day cycle

Quadruplet regimen prior to resection for pancreatic cancer

Eligibility Criteria

• Age: 18 Years - 100 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) as determined by a local laboratory (adenosquamous is also allowed).
• Tumor confined to the pancreas and deemed resectable or borderline resectable per NCCN guidelines for these criteria.
• Patients must have not received previous anti-cancer therapy for the treatment of pancreatic ductal adenocarcinoma.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function (laboratory results must be obtained within the 21-day screening window) including hematologic, renal and hepatic function.
• Absolute neutrophil count \> 1500/mm3
• Platelets \> 100,000/mm3
• Calculated creatinine clearance \> 60 mL/min (Cockcroft Gault)
• Albumin \> 3.0 g/dL
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) \< 3.0 x ULN
• Total bilirubin ≤ 1.5 X ULN
• Able to adhere to study visit schedule and other protocol requirements
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 9 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year

You may not qualify if:

• \- Diagnosis of pancreatic neuroendocrine carcinoma or pancreatic acinar cell carcinoma.
• Determined by the medical or surgical team to be a poor candidate for future surgical resection
• Has locally advanced or metastatic disease as determined by imaging
• o This includes those with a baseline CA 19-9 level \> 1000 as these subjects have a high rate of metastatic disease
• 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) for pancreatic cancer.
• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer
• Any prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1 inhibitor).
• Administration of a live vaccine within 30 days of the first dose of therapy on study
• 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 has concurrent malignancy other than the disease under investigation, with exception of malignancy that was treated curatively and has not recurred within 2 years prior to the date of screening. Fully resected basal or squamous cell skin cancers, and any carcinoma in situ are eligible.
• Subjects with a history of pneumonitis or interstitial lung disease requiring therapy
• 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.
• Known history of testing positive for Human Immunodeficiency Virus (HIV) infections.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (3)

Ambulatory Care Center

New York, New York, 10016, United States

Location

Clinical Cancer Center

New York, New York, 10016, United States

Location

NYU Langone Ambulatory Care Center East 38th Street

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Gastrointestinal Neoplasms

Interventions

canakinumab; tislelizumab; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Paul Oberstein, MD

  Perlmutter New York University Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 9, 2023
• Study Start: July 14, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request .Requests should be directed to Paul.Oberstein@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (3)