Clinical trial NCT06616584: 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)
Official title: A Randomized Phase II/III Study of Docetaxel and Ramucirumab With or Without Cemiplimab for Participants Previously Treated With Platinum-Based Chemotherapy and Immunotherapy for Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Non-Matched Sub-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Recurrent Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: Regeneron Pharmaceuticals
name: National Cancer Institute (NCI)
First posted: 2024-09-27
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From date of randomization to date of death due to any cause, assessed up to 3 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From date of randomization to date of first documentation of progression, symptomatic deterioration, or death, whichever comes first, assessed up to 3 years
measure: Response rates
timeFrame: Up to 3 years
measure: Disease control rates
timeFrame: Up to 3 years
measure: Duration of response (DOR)
timeFrame: From date of first documentation of response by RECIST 1.1 (CR or PR, confirmed or unconfirmed) to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years
measure: Incidence of adverse events
timeFrame: Up to 90 days after last dose of study treatment
Other outcomes:
measure: Cell-free deoxyribonucleic acid
timeFrame: At baseline, cycle 3 day 1 and at progression up to 3 years (each cycle is 21 days)
measure: Tissue/blood repository
timeFrame: Up to 3 years
Locations:
city: Savannah
country: United States
facility: Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
state: Georgia
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Dixon
country: United States
facility: Illinois CancerCare-Dixon
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
state: Illinois
city: Washington
country: United States
facility: Illinois CancerCare - Washington
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Cumberland
country: United States
facility: UPMC Western Maryland
state: Maryland
city: Brighton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Brighton
state: Michigan
city: Canton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Canton
state: Michigan
city: Chelsea
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
state: Michigan
city: Lansing
country: United States
facility: University of Michigan Health - Sparrow Lansing
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Pontiac
country: United States
facility: Trinity Health Saint Joseph Mercy Oakland Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
state: Michigan
city: Columbus
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Golden Triangle
state: Mississippi
city: Grenada
country: United States
facility: Baptist Cancer Center-Grenada
state: Mississippi
city: New Albany
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Union County
state: Mississippi
city: Oxford
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Oxford
state: Mississippi
city: Southhaven
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Desoto
state: Mississippi
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Farmington
country: United States
facility: Parkland Health Center - Farmington
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Sainte Genevieve
country: United States
facility: Sainte Genevieve County Memorial Hospital
state: Missouri
city: Sullivan
country: United States
facility: Missouri Baptist Sullivan Hospital
state: Missouri
city: Sunset Hills
country: United States
facility: BJC Outpatient Center at Sunset Hills
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Beaver
country: United States
facility: UPMC-Heritage Valley Health System Beaver
state: Pennsylvania
city: Butler
country: United States
facility: UPMC Hillman Cancer Center at Butler Health System
state: Pennsylvania
city: Cranberry Township
country: United States
facility: UPMC Hillman Cancer Center - Passavant - Cranberry
state: Pennsylvania
city: Erie
country: United States
facility: UPMC Hillman Cancer Center Erie
state: Pennsylvania
city: Farrell
country: United States
facility: UPMC Cancer Center at UPMC Horizon
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Centers - Arnold Palmer Pavilion
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle Cancer Center/Community Osteopathic Campus
state: Pennsylvania
city: Indiana
country: United States
facility: IRMC Cancer Center
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC-Johnstown/John P. Murtha Regional Cancer Center
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC Cancer Center at UPMC McKeesport
state: Pennsylvania
city: Mechanicsburg
country: United States
facility: UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC Hillman Cancer Center - Monroeville
state: Pennsylvania
city: Moon
country: United States
facility: UPMC Hillman Cancer Center in Coraopolis
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: UPMC Hillman Cancer Center - Part of Frick Hospital
state: Pennsylvania
city: N. Huntingdon
country: United States
facility: Arnold Palmer Cancer Center Medical Oncology Norwin
state: Pennsylvania
city: Natrona Heights
country: United States
facility: UPMC Cancer Center-Natrona Heights
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Hillman Cancer Center - New Castle
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Saint Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Passavant Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Saint Clair Hospital Cancer Center
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Cancer Center at UPMC Northwest
state: Pennsylvania
city: Washington
country: United States
facility: UPMC Cancer Center-Washington
state: Pennsylvania
city: Williamsport
country: United States
facility: UPMC Susquehanna
state: Pennsylvania
city: Williamsport
country: United States
facility: Divine Providence Hospital
state: Pennsylvania
city: Bluffton
country: United States
facility: Saint Joseph's/Candler - Bluffton Campus
state: South Carolina
city: Hilton Head Island
country: United States
facility: South Carolina Cancer Specialists PC
state: South Carolina
city: Collierville
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Collierville
state: Tennessee
city: Memphis
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Memphis
state: Tennessee
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Saint Mary's
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Saint Vincent Hospital Cancer Center at Oconto Falls
state: Wisconsin
city: Sheboygan
country: United States
facility: Saint Vincent Hospital Cancer Center at Sheboygan
state: Wisconsin
city: Sheboygan
country: United States
facility: Sheboygan Physicians Group
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: SWOG Cancer Research Network
name: Saiama N Waqar
role: PRINCIPAL_INVESTIGATOR
References: