This phase II trial studies how well docetaxel works with or without bintrafusp alfa in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). Chemotherapy drugs, such as docetaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bintrafusp alfa, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving docetaxel and bintrafusp alfa in combination may work better in treating non small-cell lung cancer compared to docetaxel alone.
PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) of bintrafusp alfa in combination with docetaxel versus (vs) docetaxel alone. SECONDARY OBJECTIVES: I. To evaluate overall survival of bintrafusp alfa in combination with docetaxel vs docetaxel alone. II. To evaluate overall response rates of bintrafusp alfa in combination with docetaxel vs docetaxel alone. III. To evaluate duration of response of bintrafusp alfa in combination with docetaxel vs docetaxel alone. IV. To evaluate the safety of bintrafusp alfa in combination with docetaxel vs docetaxel alone. CORRELATIVE RESEARCH OBJECTIVES: I. To evaluate PD-L1, TGF-beta, and TMB as potential predictive markers of clinical response in tumor biopsies and in plasma. II. To evaluate biomarkers associated with inhibition of TGF-beta and PD-L1. III. To evaluate the changes in immune system using mass cytometry in response to TGF-beta and PD-L1 inhibition. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive docetaxel intravenously (IV) over 1 hour and bintrafusp alfa IV over 60 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bintrafusp alfa IV over 60 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive docetaxel IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may crossover to Arm I and receive bintrafusp alfa alone. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given IV
Given IV
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Progression-free Survival (PFS) of Bintrafusp Alfa in Combination With Docetaxel Versus (vs) Docetaxel Alone
The primary analysis of PFS will be a comparison of the Kaplan-Meier curves for docetaxel + bintrafusp alfa vs. docetaxel alone using a one-sided log-rank test.
Time frame: From randomization to the first of either disease progression or death from any cause, assessed up to 3 years and 2 months
Overall Survival (OS)
OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
Time frame: From study entry to death from any cause, assessed up to 3 years and 2 months
Confirmed Response Rates
Will be classified as a confirmed response per the Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria, if they have a partial or complete response for 2 consecutive evaluations at least 4 weeks apart. The proportion of patients with a confirmed response will be calculated and compared between the 2 arms using a Chi-square of Fisher's Exact test.
Time frame: Up to 3 years and 2 months
Duration of Response
The duration of confirmed responses will be assessed using the Kaplan Meier method, where the duration of confirmed response will be defined as the time from the first documented date of response (complete response \[CR\] or partial response \[PR\]) to the date at which progression is first documented. Duration of response will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
Time frame: Up to 3 years and 2 months
Incidence of Adverse Events
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 3 years and 2 months
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