Purpose

This phase III trial studies whether pembrolizumab alone as a first-line treatment, followed by pemetrexed and carboplatin with or without pembrolizumab after disease progression is superior to induction with pembrolizumab, pemetrexed and carboplatin followed by pembrolizumab and pemetrexed maintenance in treating patients with stage IV non-squamous non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, 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. It is not yet known whether giving first-line pembrolizumab followed by pemetrexed and carboplatin with or without pembrolizumab works better in treating patients with non-squamous non-small cell cancer.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- Patients must have histologically or cytologically confirmed stage IV non-squamous
nonā€small cell lung cancer (NSCLC) (includes M1a, M1b, and M1c stage disease, American
Joint Committee on Cancer [AJCC] 8th edition). Patients with Stage IIIB and IIIC
disease are eligible if they are not candidates for combined chemotherapy and
radiation

- Patients must have PD-L1 expression Tumor Proportion Score (TPS) >= 1% in tumor cells.
If PD-L1 expression TPS is unevaluable or the testing could not be completed, the
patients are not eligible. The assay must have been performed by a Clinical Laboratory
Improvement Act (CLIA) (or equivalent) certified laboratory

- Patients must have measurable or non-measurable disease. The presence of malignant
pleural fluid alone is sufficient to satisfy this eligibility criterion. Baseline
imaging assessments and measurements used to evaluate all measurable or non-measurable
sites of disease must be done within 4 weeks prior to study registration

- NOTE: If patient receives pemetrexed, follow institutional guidelines to drain
fluids

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1

- Patients must NOT have received the following:

- Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC.
Patients treated with any prior checkpoint inhibitors for metastatic lung cancer
are ineligible. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy)
or immunotherapy for locally advanced Stage III disease is allowed if at least 6
months have elapsed between the last dose of the prior therapy and study
registration. Local therapy, e.g. palliative radiation, is allowed as long as a
period of 14 days has passed between completion of local therapy and study
registration. Registration prior to treatment during the 14 days is allowed.
Palliative radiation must be to non-target lesions

- Methotrexate (MTX) given in low doses for non-malignant conditions with last dose
at least 14 days prior to date of registration will be allowed. Other low dose
chemotherapeutics for non-malignant conditions will be considered, but review by
the study chair is required

- Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600)
or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors
are excluded

- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression. CNS
progression counts as progression and patients must move on to the next phase after
CNS treatment. Patients with asymptomatic new (at screening) or progressive brain
metastases (active brain metastases at screening) or leptomeningeal disease are
eligible if the treating physician determines that immediate CNS specific treatment is
not required and is unlikely to be required during the first cycle of therapy

- Patients are eligible if off steroids for at least 14 days prior to protocol
treatment

- Palliative radiation to non-target lesions (bone metastasis) is allowed if
patient develops symptoms

- Anticonvulsants are allowed

- Patients with asymptomatic, sub-centimeter brain metastasis who at the discretion
of investigators do not need immediate CNS directed therapies are eligible

- Patients with 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

- Patients must not have known pre-existing and clinically active interstitial lung
disease, or a known history of (non infectious) pneumonitis that required steroids, or
current pneumonitis

- Patients must not have significant gastrointestinal disorders with diarrhea as a major
symptom (e.g. Crohn's disease, malabsorption, etc.)

- Patients must not have history of auto-immune condition requiring ongoing or
intermittent systemic treatment in the past 2 years (i.e. with use of disease
modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment

- 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

- Patients must not have any other concomitant serious illness or organ system
dysfunction that in the opinion of the investigator would either compromise patient
safety or interfere with the evaluation of the safety of the study drug

- Patients must not receive any other investigational agents during the course of
therapy

- Women must not be pregnant or breast-feeding due to potential harm to the fetus or
infant from cytotoxic chemotherapy and the unknown risk of MK-3475 (pembrolizumab).
Patients must also not expect to conceive or father children from the time of
registration, while on study treatment, and until at least 120 days after the last
dose of study treatment

- All females of childbearing potential must have a blood test or urine study
within 72 hours prior to registration to rule out pregnancy

- A female of childbearing potential is any woman, regardless of sexual orientation
or whether they have undergone tubal ligation, who meets the following criteria:
has achieved menarche at some point; has not undergone a hysterectomy or
bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea
following cancer therapy does not rule out childbearing potential) for at least
24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months)

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception or abstain from sexual intercourse from time of
registration, while on study treatment, and continue for 120 days after the last dose
of study treatment

- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of randomization)

- Platelets >= 100,000/mm^3 (within 14 days of randomization)

- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 Or if patient on
therapeutic anticoagulation, PT/INR =< 3.0 (within 14 days of randomization)

- Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN) OR, if
patient is on therapeutic anticoagulation, PTT must be =< 1.5 x ULN (within 14 days of
randomization)

- Total bilirubin =< 1.5 mg/dL (obtained within 14 days of randomization)

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5
x upper limit of normal (ULN) (obtained within 14 days of randomization)

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x
upper limit of normal (ULN) (obtained within 14 days of randomization)

- Calculated creatinine clearance >= 45 ml/min to be eligible to receive pemetrexed
(obtained within 14 days prior to randomization)

- Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) (obtained within
14 days prior to randomization)

- Patients must not have a known history of active tuberculosis (TB)

- Patients must not have a diagnosis of immunodeficiency or receive systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of protocol treatment

- Patients must not have received a live vaccine within 30 days prior to randomization.
Seasonal flu vaccines that do not contain live virus are permitted

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable or on suppressive therapy, if indicated. Patients with a
history of hepatitis C virus (HCV) infection must have been treated and cured. For
patients with HCV infection who are currently on treatment, they are eligible if they
have an undetectable HCV viral load

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (pembrolizumab, pemetrexed, carboplatin)
Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pemetrexed IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then may receive pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate
Experimental
Arm B (pembrolizumab, pemetrexed, carboplatin)
Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate
Active Comparator
Arm C (pembrolizumab, pembrolizumab, carboplatin)
Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate

Recruiting Locations

Montefiore Medical Center-Weiler Hospital
Bronx, New York 10461
Contact:
Site Public Contact
718-379-6866
aaraiza@montefiore.org

Montefiore Medical Center-Einstein Campus
Bronx, New York 10461
Contact:
Site Public Contact
718-379-6866
aaraiza@montefiore.org

Montefiore Medical Center - Moses Campus
Bronx, New York 10467
Contact:
Site Public Contact
718-379-6866
aaraiza@montefiore.org

More Details

Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate overall survival (OS) in each of the 2 experimental arms (Arms A and B) to control (Arm C).

SECONDARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Arm C versus each of Arms A and B.

II. To evaluate best objective response rates per RECIST 1.1 for Arm C versus each of Arms A and B.

III. To estimate toxicity within each of the treatment arms via the Common Terminology Criteria for Adverse Events (CTCAE) criteria.

IV. To compare outcomes between Arms A and B. V. To compare outcomes by treatment arm within subgroups defined by a cutpoint of PD-L1 expression at >= 50%.

BIOMARKER OBJECTIVE:

I. To collect and bank tissue and blood for future research studies, including potential development of a prognostic and predictive signature for MK-3475 (pembrolizumab) in combination with chemotherapy versus MK-3475 (pembrolizumab) alone.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pemetrexed IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then may receive pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.

ARM C: Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.

After completion of study treatment, patients are followed up for 5 years.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.