Trial Title:
Adding the Immunotherapy Drug Cemiplimab to Usual Treatment for People With Advanced Non-Small Cell Lung Cancer Who Had Previous Treatment With Platinum Chemotherapy and Immunotherapy (An Expanded Lung-MAP Treatment Trial)
NCT ID:
NCT06616584
Condition:
Recurrent Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Dexamethasone
Dexamethasone acetate
Docetaxel
Cemiplimab
Ramucirumab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Lexatumumab
BB 1101
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Cemiplimab
Description:
Given IV
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Cemiplimab RWLC
Other name:
Cemiplimab-rwlc
Other name:
Libtayo
Other name:
REGN 2810
Other name:
REGN-2810
Other name:
REGN2810
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given PO
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Aacidexam
Other name:
Adexone
Other name:
Aknichthol Dexa
Other name:
Alba-Dex
Other name:
Alin
Other name:
Alin Depot
Other name:
Alin Oftalmico
Other name:
Amplidermis
Other name:
Anemul mono
Other name:
Auricularum
Other name:
Auxiloson
Other name:
Baycadron
Other name:
Baycuten
Other name:
Baycuten N
Other name:
Cortidexason
Other name:
Cortisumman
Other name:
Decacort
Other name:
Decadrol
Other name:
Decadron
Other name:
Decadron DP
Other name:
Decalix
Other name:
Decameth
Other name:
Decasone R.p.
Other name:
Dectancyl
Other name:
Dekacort
Other name:
Deltafluorene
Other name:
Deronil
Other name:
Desamethasone
Other name:
Desameton
Other name:
Dexa-Mamallet
Other name:
Dexa-Rhinosan
Other name:
Dexa-Scheroson
Other name:
Dexa-sine
Other name:
Dexacortal
Other name:
Dexacortin
Other name:
Dexafarma
Other name:
Dexafluorene
Other name:
Dexalocal
Other name:
Dexamecortin
Other name:
Dexameth
Other name:
Dexamethasone Intensol
Other name:
Dexamethasonum
Other name:
Dexamonozon
Other name:
Dexapos
Other name:
Dexinoral
Other name:
Dexone
Other name:
Dinormon
Other name:
Dxevo
Other name:
Fluorodelta
Other name:
Fortecortin
Other name:
Gammacorten
Other name:
Hemady
Other name:
Hexadecadrol
Other name:
Hexadrol
Other name:
LenaDex
Other name:
Lokalison-F
Other name:
Loverine
Other name:
Methylfluorprednisolone
Other name:
Millicorten
Other name:
Mymethasone
Other name:
Orgadrone
Other name:
Spersadex
Other name:
TaperDex
Other name:
Visumetazone
Other name:
ZoDex
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Given IV
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Docecad
Other name:
RP 56976
Other name:
RP-56976
Other name:
RP56976
Other name:
Taxotere
Other name:
Taxotere Injection Concentrate
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Ramucirumab
Description:
Given IV
Arm group label:
Arm I (ramucirumab, docetaxel)
Arm group label:
Arm II (cemiplimab, ramucirumab, docetaxel)
Other name:
Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B
Other name:
Cyramza
Other name:
IMC 1121B
Other name:
IMC-1121B
Other name:
IMC1121B
Other name:
LY 3009806
Other name:
LY-3009806
Other name:
LY3009806
Other name:
Monoclonal Antibody HGS-ETR2
Summary:
This phase II/III Expanded Lung-MAP treatment trial compares the effect of adding
cemiplimab to docetaxel and ramucirumab versus docetaxel and ramucirumab alone in
treating patients with non-small cell lung cancer that is stage IV or that has come back
after a period of improvement (recurrent). Cemiplimab is a monoclonal antibody that
stimulates the immune system by blocking the PD-1 pathway. Tumors use the PD-1 pathway to
escape attacks from the immune system. By blocking the PD-1 pathway, cemiplimab may help
the immune system recognize and attack tumor cells. Docetaxel is in a class of
medications called taxanes. It stops tumor cells from growing and dividing and may kill
them. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood
vessels that tumors need to grow. Adding cemiplimab to usual treatment, docetaxel and
ramucirumab, may kill more tumor cells compared to docetaxel and ramucirumab alone in
treating patients with stage IV or recurrent non-small cell lung cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare overall survival (OS) between participants randomized to docetaxel and
ramucirumab with or without cemiplimab (REGN2810) who have acquired resistance to
platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell
lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To compare investigator-assessed progression-free survival (PFS) per Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the arms.
II. To compare investigator-assessed response rates (confirmed or unconfirmed, complete
response [CR] or partial response [PR]) per RECIST 1.1 between the arms among
participants with measurable disease.
III. To compare the investigator-assessed disease control rate (confirmed or unconfirmed,
complete response [CR], or partial response [PR], and stable disease) between the arms.
IV. To evaluate the duration of response (DoR) among responders within each arm.
V. To evaluate the frequency and severity of toxicities within each arm. VI. To compare
investigator-assessed PFS between the arms within the subgroups defined by the
stratification factors (histology and performance status) and by PD-L1 subgroups defined
as PD-L1 negative (< 1% tumor proportion score [TPS]), intermediate PD-L1 (1-49% TPS),
and PD-L1 high (>= 50% TPS).
VII. To compare OS between the arms within the subgroups defined by the stratification
factors (histology and performance status) and by PD-L1 subgroups defined as PD-L1
negative (< 1% TPS), intermediate PD-L1 (1-49% TPS), and PD-L1 high (>= 50% TPS).
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at baseline,
cycle 3 day 1, and progression for future development of a proposal to evaluate
comprehensive next-generation sequencing of circulating tumor DNA (ctDNA).
II. To establish a tissue/blood repository to pursue future studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive dexamethasone orally (PO) twice daily (BID) on days 0-2,
ramucirumab intravenously (IV) over 30-60 minutes on day 1 and docetaxel IV over 60
minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Additionally, patients undergo blood sample
collection, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout
the study.
ARM II: Patients receive dexamethasone PO BID on days 0-2, ramucirumab IV over 30-60
minutes on day 1, docetaxel IV over 60 minutes on day 1, and cemiplimab IV over 30
minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Additionally, patients undergo blood sample
collection, and CT or MRI throughout the study.
After completion of study treatment, patients are followed up every 3-6 months for up to
3 years after randomization.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have been assigned to S1800E by the Southwest Oncology Group
(SWOG) Statistics and Data Management Center (SDMC). Assignment to S1800E is
determined by the LUNGMAP protocol
- Participants must have measurable or non-measurable disease documented by CT or MRI.
The CT from a combined positron emission tomography (PET)/CT may be used to document
only non-measurable disease unless it is of diagnostic quality. Measurable disease
must be assessed within 28 days prior to randomization. Pleural effusions, ascites
and laboratory parameters are not acceptable as the only evidence of disease.
Non-measurable disease must be assessed within 42 days prior to randomization. All
disease must be assessed and documented on the Baseline Tumor Assessment Form.
Participants whose only measurable disease is within a previous radiation therapy
port must demonstrate clearly progressive disease (in the opinion of the treating
investigator) prior to registration
- Participants must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to randomization
- Participants must have received exactly one anti-PD-1 or anti-PD-L1 therapy for
advanced disease (stage IV or recurrent disease, or stage I-III disease in certain
circumstances outlined below). Anti-PD-1 or anti-PD-L1 therapy may have been given
alone or in combination with other therapy. For participants who received
neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy for
stage I-III disease:
- If they experienced disease progression within (≤) 365 days from initiation
(cycle 1 day 1) or anti-PD-1 or anti-PD-L1 therapy, this counts as the single
allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease
- If they experienced disease progression more than (>) 365 days from initiation
(cycle 1 day 1) or anti-PD-1 or anti-PD-L1 therapy, this is not considered
anti-PD-1 or anti-PD-L1 therapy for advance disease. These participants must
have received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease
- Participants must have experienced disease progression (in the opinion of the
treating investigator) more than (>) 84 days following initiation (cycle 1 day 1) of
their most recent anti-PD-1 or anti-PD-L1 therapy
- Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent
disease must have had a best response of stable disease, partial response or
complete response (in the opinion of the treating investigator) on the anti-PD-1 or
anti-PD-L1 therapy for stage IV or recurrent disease
- Participants must have received platinum-based chemotherapy and experienced disease
progression (in the opinion of the treating investigator) during or after this
regimen
- Participants with a known sensitizing molecular alteration for which a Food and Drug
Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK,
ROS1, BRAF, RET, NTRK, KRAS, HER2, and MET sensitizing mutations), must have
previously received at least one of the approved therapy(s). Prior targeted therapy
for participants with targetable alterations is allowed if all other eligibility
criteria are also met
- Participants must have recovered (≤ grade 1) from any side effects from the most
recent anti-cancer treatment prior to randomization
- Participants must not have received prior therapy with docetaxel for this disease
- Participants must not have received any palliative radiation therapy within 14 days
(or palliative bone radiation therapy within 7 days) prior to randomization
- Participants must not be planning to receive any concurrent chemotherapy,
immunotherapy, or biologic therapy for cancer treatment while receiving treatment on
this study
- Participants must not have undergone major surgery within 28 days prior to
randomization, or subcutaneous venous access device placement within 7 days prior to
randomization. Participants must not have postoperative bleeding complications or
wound complications from a surgical procedure performed within 2 months prior to
randomization. The participant must not have elective or planned major surgery to be
performed during the course of this study
- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to randomization)
- Hemoglobin ≥ 9.0 g/dL (within 28 days prior to randomization)
- Platelets ≥ 100 x 10^3/uL (within 28 days prior to randomization)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days
prior to randomization) unless history of Gilbert's disease. Participants with
history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x
institutional ULN (within 28 days prior to randomization). Participants with history
of liver metastasis must have AST and ALT ≤ 5 x ULN
- Participants must have a creatinine ≤ the institutional (I)ULN or calculated
creatinine clearance ≥ 50 mL/min using the following Cockcroft-Gault formula. This
specimen must have been drawn and processed within 28 days prior to randomization
- Participants must have a urinary protein test performed within 28 days prior to
randomization
- Participants' most recent Zubrod/Eastern Cooperative Oncology Group (ECOG)
performance status must be 0-1 and be documented within 28 days prior to
randomization
- Participants must have a completed medical history and physical exam within 28 days
prior to randomization
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load while on suppressive therapy on the most recent test
results obtained within 6 months prior to randomization, if indicated by the
treating investigator
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants currently being treated for HCV infection must have
undetectable HCV viral load test on the most recent test results obtained within 6
months prior to randomization, if indicated by the treating investigator
- Participants with known human immunodeficiency virus (HIV) infection are eligible,
provided they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test and within 6 months prior to randomization
- Participants must not have a prior or concurrent malignancy whose natural history or
treatment has the potential to interfere with the safety or efficacy assessment of
the investigational regimen
- Participants must not have an active autoimmune disease that has required systemic
treatment within 730 days prior to randomization (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) is not considered a form of systemic treatment
and is allowed
- Participants must not have any history of primary immunodeficiency
- Participants must be able to safely receive study therapy and must not have
experienced the following:
- Any grade 3 or worse immune-mediated adverse event. Exception: asymptomatic
nonbullous/nonexfoliative rash
- Any unresolved grade 2 immune-mediated adverse event
- Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1
immunotherapy
- Exception to the above: Toxicities of any grade that requires replacement
therapy and has stabilized on therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) are
allowed
- Participants must not have any history of organ transplant that requires use of
immunosuppressives
- Participants must not have received a live or live attenuated vaccine within 28 days
prior to randomization. Examples of live vaccines include, but are not limited to,
the following: measles, mumps, rubella, varicella/zoster, yellow fever rabies,
Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and
COVID-19 vaccines are allowed, however, intranasal influenza vaccines (e.g.
Flu-Mist) are live attenuated and are not allowed
- Participants must not have clinical signs or symptoms of active tuberculosis
infection
- Participants must not have a history of (non-infectious) pneumonitis that required
steroids or current pneumonitis/interstitial lung disease
- Participants must not have had a serious or nonhealing wound, ulcer, or bone
fracture within 28 days prior to randomization
- Participants must not have a history of gastrointestinal perforation or fistula
within 6 months prior to randomization
- Participants must not have grade 3-4 gastrointestinal bleeding (defined by National
Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]
version [v]5) within 3 months prior to randomization. No history of gastrointestinal
(GI) bleed within 3 months prior to randomization
- Participants must not have any grade III/IV cardiac disease as defined by the New
York Heart Association criteria (i.e., participants with cardiac disease resulting
in marked limitation of physical activity or resulting in inability to carry on any
physical activity without discomfort), unstable angina pectoris, and myocardial
infarction within 6 months prior to randomization, or serious uncontrolled cardiac
arrhythmia
- Participants must not have experienced any arterial thromboembolic events, including
but not limited to myocardial infarction, transient ischemic attack, cerebrovascular
accident, or unstable angina, within 6 months prior to randomization
- Participants must not have gross hemoptysis within two months prior to randomization
(defined as bright red blood or ≥ 1/2 teaspoon) or with radiographic evidence of
intratumor cavitation or has radiologically documented evidence of major blood
vessel invasion or encasement by cancer
- Participants must not have been diagnosed with venous thrombosis within 3 months
prior to randomization. Participants with venous thrombosis diagnosed more than 3
months prior to randomization must be on stable doses of anticoagulants
- Participants must not have cirrhosis at a level of Child-Pugh B (or worse) AND a
history of hepatic encephalopathy or clinically meaningful ascites resulting from
cirrhosis, OR any degree of cirrhosis
- Participants must not be pregnant or breastfeeding (nursing includes breast milk fed
to an infant by any means, including from the breast, milk expressed by hand, or
pumped). Individuals who are of reproductive potential must have agreed to use an
effective contraceptive method with details provided as a part of the consent
process. A person who has had menses at any time in the preceding 12 consecutive
months or who has semen likely to contain sperm is considered to be of "reproductive
potential." In addition to routine contraceptive methods, "effective contraception"
also includes refraining from sexual activity that might result in pregnancy and
surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal
ligation/occlusion, and vasectomy with testing showing no sperm in the semen
- Participants must agree to have blood specimens submitted for circulating tumor DNA
(ctDNA)
- Participants must be offered participation in specimen banking. With participant
consent, specimens must be collected and submitted via the SWOG specimen tracking
system
- NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration
process the treating institution's identity is provided in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered in the system
- Participants must be informed of the investigational nature of this study and
must sign and give informed consent in accordance with institutional and
federal guidelines. NOTE: Participants with impaired decision-making
capabilities, legally authorized representatives may sign and give informed
consent on behalf of study participants in accordance with applicable federal,
local, and Central Institutional Review Board (CIRB) regulations
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
July 11, 2025
Completion date:
December 31, 2028
Lead sponsor:
Agency:
SWOG Cancer Research Network
Agency class:
Other
Collaborator:
Agency:
Regeneron Pharmaceuticals
Agency class:
Industry
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
SWOG Cancer Research Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06616584
