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
Overview
- Phase
- Phase 1
- Intervention
- Canakinumab
- Conditions
- Pancreatic Cancer
- Sponsor
- NYU Langone Health
- Enrollment
- 9
- Locations
- 3
- Primary Endpoint
- Number of patients who proceeded to surgical resection
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-
- •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
Exclusion Criteria
- •\- 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.
Arms & Interventions
Quadruplet regimen prior to resection for pancreatic cancer
Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)
Intervention: Canakinumab
Quadruplet regimen prior to resection for pancreatic cancer
Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)
Intervention: Tislelizumab
Quadruplet regimen prior to resection for pancreatic cancer
Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)
Intervention: Nab-Paclitaxel
Quadruplet regimen prior to resection for pancreatic cancer
Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Number of patients who proceeded to surgical resection
Time Frame: End of treatment (up to 6 months)
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.
Number of dose limiting toxicities (DLTs)
Time Frame: 56 days
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.
Secondary Outcomes
- Number of delays outcome of surgery that is attributed to study drug(At surgery post treatment (up until 6 months))
- Progression Free Survival (PFS)(Up to 6 months after patients last treatment)
- Number of changes in outcome of surgery that is attributed to study drug(At surgery post treatment (up until 6 months))
- Overall Response Rate (ORR)(Up to 6 months post treatment)
- R0 resection rate (R0)(At surgery post treatment (up until 6 months))
- Overall Survival (OS)(Up to 6 months after patients last treatment)