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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Given IV
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of adverse events (AEs), serious AEs
Time frame: Up to 4 years
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
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
PD-L1 expression
Time frame: Up to 4 years
Phosphorylated or total STAT3 expression levels
Time frame: Up to 4 years
Characterization of immune infiltrates
Time frame: Up to 4 years
Quantification and characterization of CD8 staining pattern
Time frame: Up to 4 years
PD-L1 protein levels in the membrane of circulating tumor cells
Time frame: Baseline up to 4 years
Physiological parameters
Vital signs will required at screening before dosing on Day -7 of the Lead-in; before dosing on Days 1, 8, 15, and 22 of each cycle; and at the EOT visit.
Time frame: Up to 4 years
Physical Examinations
A complete physical examination is required at screening, before dosing on Day 7 of the Lead in, before dosing on Day 1 of each cycle, and at the EOT visit. A targeted physical examination as directed by disease, signs and symptoms is required before dosing on Day 15 of each cycle.
Time frame: Up to 4 years
Disease control
Will be defined as a compete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Time frame: At 4 months
Objective response
Will be defined as a CR or PR according to RECIST version 1.1.
Time frame: Up to 4 years
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
Best overall response (including CR, PR, SD, and progressive disease [PD], according to RECIST version 1.1 criteria)
Time frame: Up to 4 years
Progression free survival
Time frame: From allocation assessed up to 4 years
Overall survival
Time frame: From start of treatment assessed up to 4 years
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