Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer

Brief summary public domain (ClinicalTrials.gov)

This phase II trial studies how well danvatirsen and durvalumab work in treating patients with pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal cancer that has spread to other places in the body and does not respond to treatment. Danvatirsen may be used to block the production of proteins needed for tumor cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving danvatirsen and durvalumab may work better at treating pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal cancer.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. Evaluate disease control rate (DCR) at 4 months. II. Evaluate tumor-based biomarkers in paired pre and post treatment biopsies (10 in each arm, 30 total) that may correlate with treatment or prospectively identify patients likely to respond to treatment with danvatirsen (AZD9150) in combination with durvalumab (MEDI4736) (may include PD-L1 expression, phosphorylated or total STAT3 expression, tumor genetics, characterization of immune infiltrates, or other stratification markers). III. Explore the relationship between PD-L1 protein levels in the membrane of circulating tumor cells obtained by peripheral blood draws prior to, during, and after treatment with clinical endpoints including treatment efficacy and toxicity. SECONDARY OBJECTIVES: I. Evaluate the frequency of dose limiting toxicities. II. Evaluate frequency of objective response (as defined as partial response \[PR\] or complete response \[CR\] according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria). III. Evaluate duration of response (DOR) measured from the time measurement criteria are first met for CR or PR, whichever is first recorded, until the first date that recurrent or progressive disease (PD) is objectively documented. IV. Evaluate best overall response (including CR, PR, stable disease \[SD\], and PD, according to RECIST version 1.1 criteria). V. Evaluate progression free survival (PFS) from allocation to the first documentation of PD as determined by the investigator or death from any cause, whichever occurs first. EXPLORATORY OBJECTIVES: I. Explore the relationship between radiologic metrics (radiomics) prior to, during, and after treatment with clinical endpoints including treatment efficacy and toxicity. OUTLINE: Patients receive danvatirsen intravenously (IV) over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, 1-3 months, then every 2 months thereafter.

Intervention public domain (ClinicalTrials.gov)

Drug: Danvatirsen. Given IV

Intervention public domain (ClinicalTrials.gov)

Biological: Durvalumab. Given IV

Arm public domain (ClinicalTrials.gov)

Treatment (danvatirsen, durvalumab) (experimental): Patients receive danvatirsen IV over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of adverse events (AEs), serious AEs. Time frame: Up to 4 years.

Primary outcome public domain (ClinicalTrials.gov)

Physiological parameters (Laboratory evaluations). Blood samples for routine coagulation assessments will be obtained at screening and once during week 4 of cycle 1. Time frame: Up to 4 years.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of treatment-emergent AEs (TEAEs), SAEs and death(s). Will be graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03. Time frame: Up to 4 years.

Primary outcome public domain (ClinicalTrials.gov)

PD-L1 expression. Time frame: Up to 4 years.

Primary outcome public domain (ClinicalTrials.gov)

Phosphorylated or total STAT3 expression levels. Time frame: Up to 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Disease control. Time frame: At 4 months.

Secondary outcome public domain (ClinicalTrials.gov)

Objective response. Time frame: Up to 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of response according to RECIST version 1.1 criteria. Time frame: From the time measurement criteria are first met for CR or PR, assessed up to 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Best overall response (including CR, PR, SD, and progressive disease [PD], according to RECIST version 1.1 criteria). Time frame: Up to 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Progression free survival. Time frame: From allocation assessed up to 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival. Time frame: From start of treatment assessed up to 4 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * The patient/legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the United States of America \[USA\]; European Union Data Privacy Directive in the European Union \[EU\]) before any study-specific procedures, including screening evaluations, sampling, and analyses * Has a histological confirmation of pancreatic cancer, mismatch deficient colorectal cancer, or non-small cell lung cancer (NSCLC) that is refractory to standard therapy or for which no standard of care regimen currently exists * Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) score of 0 or 1 * Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerized tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy * Transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted * Leukocytes \>= 3000 mcL * Absolute neutrophil count \>= 1500 mcL * Platelets \> = 100 000 mcL * Hemoglobin \>= 9 g/dL * Total bilirubin =\< 1.5 x upper limit of normal (ULN) * Total bilirubin =\< 3 x ULN in patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or in the presence of liver metastases * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN if no demonstrable liver metastases or =\< 5 x ULN in the presence of liver metastases * Creatinine within normal limits OR, for patients with levels above institutional normal: creatinine clearance measured by 24-hour urine collection \>= 60 mL/min, OR calculated corrected creatinine clearance \>= 60 mL/min/1.73 m\^2 using the Cockcroft-Gault formula (Cockcroft and Gault 1976) corrected for the body surface area * Women of childbearing potential and men who are sexually active with a female partner of childbearing potential must be surgically sterilized, practicing abstinence, or agree to use 2 birth control methods before study entry, for …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 39 participants (actual).