Chemotherapy and Pembrolizumab in Treating Patients with Stage IV Non-small Lung Cancer Previously Treated with PD-1 or PD-L1 Inhibitor
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of protected health information; NOTE: HIPAA authorization may be included in the informed consent or obtained separately
- Histological or cytological evidence of stage IV non-small cell lung cancer (NSCLC) (any histology)
- Subjects must have progressed on or after previous platinum-based chemotherapy; Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor; subjects must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including pembrolizumab) as their most recent therapy and must have had at least a 3-month PFS on this therapy
- Subjects must be enrolled on the trial within 12 weeks of their last infusion of PD-1 or PD-L1 inhibitor therapy
- Subjects whose tumors harbor a mutation in EGFR exon 19 or 21 or have gene rearrangements in ALK or ROS1 must have already been treated with standard targeted therapies; NOTE: Subjects must also have progressed on or after platinum containing combination chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy
- Must be fit enough to receive next-line chemotherapy (either gemcitabine, docetaxel, or pemetrexed [non-squamous only]) according to the discretion of the treating physician
- Absolute neutrophil count (ANC) >= 1,500 K/mm^3 (within 28 days prior to registration for protocol therapy)
- Platelets >= 100,000 K/mm^3 (within 28 days prior to registration for protocol therapy)
- Hemoglobin without transfusion or epoetin alfa (EPO) dependency (within 7 days of assessment) >= 9 g/dL or >= 5.6 mmol/L
- Serum 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]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (within 28 days prior to registration for protocol therapy)
- Serum total bilirubin => 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 28 days prior to registration for protocol therapy)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN (within 28 days prior to registration for protocol therapy)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy; in the case of anticoagulants, PT/INR/partial thromboplastin time (PTT) must be within therapeutic range of intended use of anticoagulants (within 28 days prior to registration for protocol therapy)
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy; in the case of anticoagulants, PT/INR/PTT must be within therapeutic range of intended use of anticoagulants (within 28 days prior to registration for protocol therapy)
- Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test within 7 days prior to study registration and/or within 72 hours of first dose of study drugs; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; female subjects will be considered of childbearing potential unless they are either: * Postmenopausal--defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient; OR * Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR * Have a congenital or acquired condition that prevents childbearing
- Women of childbearing potential must be willing to use two methods of contraception or abstain from heterosexual activity from the point of registration through 120 days after the last dose of study drug
- Male subjects capable of fathering a child must agree to use an adequate method of contraception starting with the first dose of the study drug through 120 days after the last dose of the study drug; male subjects will be considered to be capable of fathering a child unless they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition)
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Active central nervous system (CNS) metastases * NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) within 28 days prior to registration to exclude brain metastases * NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off corticosteroids for >= 2 weeks, are asymptomatic, and there is no evidence of progression on brain imaging (CT or MRI)
- Treatment with any investigational agent within 28 days prior to registration for protocol therapy with the exception of PD-1 or PD-L1 inhibitors
- No active second cancers with the exception of localized non-melanoma skin cancer, in-situ cervical or in-situ bladder cancer
- Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; NOTES: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren’s syndrome will not be excluded.
- Prior solid organ or stem cell transplant.
- History of interstitial lung disease or pneumonitis related to the use of immunotherapeutic drugs. Subjects with a history of pneumonitis which is unrelated to the use of immunotherapeutic drugs may participate at the discretion of the treating physician.
- History of an immune-related toxicity requiring treatment with corticosteroids during prior PD-1/ PD-L1 inhibitor treatment
- Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of study registration
- History of psychiatric illness or social situations that would limit compliance with study requirements
- Clinically active infection (>= grade 2) as judged by the site investigator
- Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C; NOTE: HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) testing is not required
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator
- Known history of active TB (Bacillus tuberculosis)
- History of hypersensitivity to pembrolizumab, docetaxel, gemcitabine, pemetrexed or any of their excipients
- Has received a live vaccine within 30 days prior to planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
I. To assess whether continuation of pembrolizumab in combination with next-line chemotherapy (either gemcitabine hydrochloride [gemcitabine], docetaxel, or pemetrexed disodium [pemetrexed] [non-squamous only]) will prolong progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients who previously benefited from a PD-1/PD-L1 inhibitor (PFS >= 3 months) but now have progressive disease as compared to historical controls.
I. To estimate PFS by immune-related RECIST (irRECIST).
II. To estimate overall response rate (ORR) by RECIST 1.1 and irRECIST criteria.
III. To estimate clinical benefit rate as defined by RECIST 1.1 and irRECIST.
IV. To estimate overall survival (OS).
V. Assess the toxicity of pembrolizumab in combination with next-line chemotherapy (gemcitabine, docetaxel, or pemetrexed [non-squamous only]).
I. To assess tumor PD-L1 status at baseline (prior to initial treatment with PD-1 inhibitor), at time of progression on PD-1 or PD-L1 inhibitor (study entry), and at time of progression on combination of pembrolizumab and chemotherapy (safety follow up visit).
II. To correlate ORR, PFS, and clinical benefit rate with the results of proteomic analysis and lipidomic profiling.
III. To correlate ORR, PFS, and clinical benefit rate with the results of NeoTYPE Lung Tumor Profile Genetic Analysis.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV on days 1 and 8, docetaxel IV on day 1, or pemetrexed disodium IV on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days, and then every 3 months for 2 years.
Trial Phase Phase II
Trial Type Treatment
Indiana University / Melvin and Bren Simon Cancer Center
- Primary ID BTCRCLUN15-029
- Secondary IDs NCI-2017-01947, 1701894485
- Clinicaltrials.gov ID NCT03083808