Summary

This phase II trial studies how well docetaxel, ramucirumab, and pembrolizumab works for the treatment of non-small cell lung cancer that has spread to other places in the body (metastatic) or has come back (recurrent) in patients who have progressed on platinum-doublet and PD-1/PD-L1 blockade therapy. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ramucirumab may block new blood vessel growth to reduce tumor growth. Immunotherapy with pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving docetaxel, ramucirumab, and pembrolizumab may work better in shrinking lung cancer.

Objectives

PRIMARY OBJECTIVE:
I. To determine the anti-tumor efficacy of the combination treatment using the 6-month progression free survival rate (6-month PFS rate) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

SECONDARY OBJECTIVES:
I. To determine the safety profile and tolerability of docetaxel and ramucirumab in combination with pembrolizumab in patients who progressed on platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor given sequentially or in combination.
II. To determine immune related adverse events of the combination docetaxel, ramucirumab, and pembrolizumab.
III. To assess the overall response rate (ORR) of the combination docetaxel, ramucirumab, and pembrolizumab.
IV. To assess the overall survival (OS) of the combination docetaxel, ramucirumab, and pembrolizumab.

EXPLORATORY OBJECTIVES:
I. To correlate treatment response with PD-L1 22C3 expression, STK11 and KRAS mutation status.
II. To correlate treatment response with the doublet tumor mutation burden (TMB) and PD-L1 22C3 expression.
III. To perform an immunophenotypic analysis of circulating immune cells by mass cytometry before and after treatment and end of treatment (EOT).
IV. To analyze the tumor infiltrating immune cells by mass cytometry coupled to blood mass cytometry, in paired biopsies before and at the end of treatment.

OUTLINE:
Patients receive docetaxel intravenously (IV) over 60 minutes, ramucirumab IV over 60 minutes, and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan throughout the trial. Patients may also undergo collection of blood and tissue samples throughout the trial.

After completion of study treatment, patients are followed up at 30 days, 12 weeks for 2 years, every 6 months for 3 years, and then annually for up to 10 years.

Eligibility

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of non-small cell lung cancer will be enrolled in this study
2. Patients must have progressed on a platinum-based chemotherapy and any of the Food and Drug Administration (FDA)-approved PD-1 or PD-L1 immune checkpoint inhibitors, either given sequentially or in combination
3. A male participant must agree to use a contraception during the treatment period plus an additional 120 days after the last dose of study treatment and refrain from donating sperm during this period
4. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR * A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days plus 30 days (a menstruation cycle) after the last dose of study treatment
5. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
6. Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
8. Life expectancy > 12 weeks as determined by the investigator
9. Absolute neutrophil count (ANC) >= 1500/uL (collected within 10 days prior to the start of study treatment)
10. Platelets >= 100 000/uL (collected within 10 days prior to the start of study treatment)
11. Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 10 days prior to the start of study treatment) * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
12. Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (collected within 10 days prior to the start of study treatment) * Creatinine clearance (CrCl) should be calculated per institutional standard
13. Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (collected within 10 days prior to the start of study treatment)
14. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (collected within 10 days prior to the start of study treatment
15. Palliative radiotherapy (to bone or soft tissue lesions) must be completed > 1 week prior to start of study drug (exception: palliative radiotherapy for pain may be used any time prior to first dose)
16. Clinically significant toxic effect(s) of the most recent prior anti-cancer therapy must be grade 1 or resolved (except alopecia and sensory neuropathy); patients with grade 2 adrenal insufficiency related to prior anti-cancer therapy (defined as requiring medical intervention, such as concomitant steroids) or grade 2 hypothyroidism (defined as requiring hormone replacement therapy) may be enrolled provided that clinical symptoms are adequately controlled and the daily dose is 10 mg or less of prednisone or equivalent. If the patient received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention
17. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
18. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

Treatment Sites in Georgia