Phase II Trial Evaluating the Safety and Efficacy of Atezolizumab in Combination with Cabozantinib for the Treatment of Metastatic, Refractory Pancreatic Cancer
Pancreatic cancer is one of the leading causes of cancer deaths in the United States with limited treatment options, especially for those patients with metastatic disease. Combination treatment with cabozantinib and atezolizumab, has demonstrated safety for the treatment of other cancers and has shown promise in preclinical studies utilizing patient derived pancreas organoids. In this study, patients with refractory, metastatic pancreatic cancer will receive combination cabozantinib + atezolizumab and the efficacy of this treatment will be assessed through overall response rate (ORR), disease control rate (DCR), median overall survival (mOS), and median progression free survival (mPFS). Safety and tolerability of combination cabozantinib plus atezolizumab in metastatic pancreatic cancer patients will also be assessed and immune profiling pre- and post-treatment will be explored.
• Stage IV pancreatic adenocarcinoma, confirmed by histology or cytology. (Note: the primary pancreatic adenosarcoma must be confirmed by histology or cytology. The stage IV metastatic disease does not necessarily need to be confirmed by histology or cytology).
• Clinical and/or radiographic progression on and/or intolerance to and/or ineligibility for treatment with at least one of the following: a fluoropyrimidine or gemcitabine based chemotherapy treatment regimens
• Radiographically measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Images (MRI or CT Scan) must be completed within 28 days prior to treatment start.
• Age ≥ 18 years
• Patients who progress on adjuvant treatment and develop metastatic disease within \< 6 months of adjuvant therapy will be considered as having one prior line of treatment and may be eligible pending subject meeting all other inclusion/exclusion criteria.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
∙ Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support.
‣ White blood cell count ≥ 2500/µL
‣ Platelets ≥ 100,000/µL without transfusion.
‣ Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
‣ Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions:
∙ Patients with documented liver metastases: AST and ALT ≤ 5 x ULN Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
‣ Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
‣ Serum albumin ≥ 2.8 g/dl
‣ (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN
‣ Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation:
∙ Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85
∙ Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
• For patients receiving therapeutic anticoagulation, they must have a stable anticoagulant regimen.
• No clinically significant hypertension as per treating physician or if hypertension, adequate control with anti-hypertensives
• Negative hepatitis B surface antigen (HBsAg) test at screening
⁃ Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
⁃ ECOG performance status ≤ 1
⁃ Recovered to baseline or to CTCAE v5.0 ≤ Grade 1 treatment-related toxicity from prior therapies
⁃ At least two weeks since last dose of prior treatment
⁃ Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment.
⁃ Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site.
⁃ Ability to understand and the willingness to sign a written informed consent