Clinical trial NCT05642572: Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)
Official title: A Randomized Phase II Study of INC280 (Capmatinib) Plus Osimertinib With or Without Ramucirumab in Participants With EGFR-Mutant, MET-Amplified Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Sub-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-12-08
Enrollment: 66
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 Lung-MAP treatment trial test the combination of targeted drugs (capmatinib, osimertinib, and/or ramucirumab) in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has EGFR and MET gene changes. Capmatinib and osimertinib are in a class of medications called kinase inhibitors. They work by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells and may help shrink tumors. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving capmatinib, osimertinib, and/or ramucirumab and targeting abnormal gene changes in tumor cells may be effective in shrinking or stabilizing advanced non-small cell lung cancer.

Detailed description: PRIMARY OBJECTIVE:

I. To compare investigator-assessed progression-free survival (IA-PFS) between participants with EGFR mutated, MET amplified non-small cell lung cancer (NSCLC) randomized to INC280 (capmatinib) and osimertinib with or without ramucirumab.

SECONDARY OBJECTIVES:

I. To evaluate if the combination of INC280 (capmatinib), osimertinib and ramucirumab or INC280 (capmatinib) and osimertinib during the first cycle of treatment has an acceptable toxicity rate.

II. To evaluate the frequency and severity of toxicities within the arms. III. To compare IA-PFS between the arms, in the subset of participants with centrally-confirmed MET amplification in tissue.

IV. To compare IA-PFS between the arms, in the subset of participants with centrally-confirmed MET amplification based on circulating tumor deoxyribonucleic acid (ctDNA).

V. To compare IA-PFS between the randomized arms in the subsets of participants with and without history of brain metastases.

VI. To compare the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) between the arms among participants with measurable disease at baseline.

VII. To compare overall survival between the arms. VIII. To compare IA-PFS between the randomized arms in the subsets of patients who have received only 1 prior line of therapy and those who have received 2 or more prior lines of therapy.

IX. To evaluate duration of response among responders within each arm.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (ctDNA) prior to treatment (Cycle 1 Day 1), Cycle 1 Day 15, Cycle 3 Day 1, and first progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA).

II. To establish a tissue/blood repository from participants with refractory non-small cell lung cancer (NSCLC).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive capmatinib orally (PO), osimertinib PO, and ramucirumab intravenously (IV) on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.

ARM B: Patients receive capmatinib PO and osimertinib PO on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.

Eligibility criteria: Inclusion Criteria:

* Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
* Participants must have been assigned to S1900G by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900G is determined by the LUNGMAP protocol
* Participants must have documentation of NSCLC with a sensitizing EGFR mutation and have radiologically or clinically progressed (in the opinion of the treating physician) on osimertinib, alone or in combination with other agent(s), as their most recent line of therapy. Any number of prior lines of therapy is allowed
* Participants must have a MET amplification determined by tissue-based or blood-based (circulating tumor DNA \[ctDNA\]) next generation sequencing (NGS) assay. MET amplifications may have been determined based on tissue submitted for testing by Foundation Medicine Inc (FMI) through the LUNGMAP screening protocol or using test results completed outside of the study. Tissue or blood must be obtained after disease progression on osimertinib (alone or in combination with another agent\[s\]). The testing must be done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO)/Independent Ethics Committee (IEC), College of American Pathologists (CAP), or similar certification

  * Note: Participants previously tested for and determined to have MET amplified NSCLC, at the time of progression on osimertinib, outside of LUNGMAP, must also submit tissue for central FMI testing on the LUNGMAP screening protocol, if available
* Participants must have either measurable disease or non-measurable disease documented by CT or MRI. The CT from a combined 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 sub-study randomization. Non-measurable disease must be assessed within 42 days prior to sub-study randomization. All known sites of 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 sub-study randomization to be considered measurable
* Participants must have a CT with contrast or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study randomization
* Participants with symptomatic CNS metastasis (brain metastases or leptomeningeal disease) must be neurologically stable and have a stable or decreasing corticosteroid requirement for at least 5 days before sub-study randomization
* Participants must have recovered (=\< grade 1) from any side effects of prior therapy, except for alopecia and vitiligo
* Participants must be able to swallow tablets whole
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to sub-study randomization)
* Hemoglobin \< 9.0 g/dL (within 28 days prior to sub-study randomization)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to sub-study randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to sub-study randomization). Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN. Participants with history of liver metastasis must have AST =\< 5 x ULN (within 28 days prior to sub-study randomization)
* Participants must have a serum creatinine =\< the IULN 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 sub-study randomization
* Participants' most recent Zubrod performance status must be 0-1 and be documented within 28 days prior to sub-study randomization
* Participants must have an electrocardiogram (ECG) performed, with a Fridericia's Correction Formula (QTcF) =\< 470 msec, within 28 days prior to sub-study randomization. It is suggested that a local cardiologist review the QTcF intervals
* Participants must have a completed medical history and physical exam within 28 days prior to sub-study randomization
* Participants must have a urinalysis performed 28 days prior to sub-study randomization. Participant must have a urinary protein =\< 1+ on dipstick or routine urinalysis (UA). Random analysis of urine protein with a normal value is sufficient. If urine dipstick or routine analysis indicated proteinuria \>= 2+, then a 24-hour urine is to be collected and demonstrate \< 2000 mg of protein in 24 hours to allow participation in the study
* Participants must have an International Normalized Ratio (INR) =\< 1.5 seconds above the institutional upper limit of normal (IULN) (unless receiving anticoagulation therapy) documented within 28 days to sub-study randomization. Participants must have a partial thromboplastin time (PTT) =\< 5 seconds above the 'institutional upper limit of normal (IULN) (unless receiving anticoagulation therapy) documented within 28 days prior to sub-study randomization
* Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load within 6 months prior to sub-study randomization
* Participants must have asymptomatic serum amylase =\< 2 x ULN and serum lipase =\< ULN obtained within 28 days prior to sub-study randomization. Asymptomatic is defined as having no signs and/ or symptoms suggesting pancreatitis or pancreatic injury (e.g. elevated P. amylase, abnormal imaging findings of pancreas, etc.)
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
* Participants must also 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 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
* Participants with impaired decision-making capacity must not have a neurological or psychological condition that precludes their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator). For 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

Exclusion Criteria:

* Participants must not have received an anti-VEGF or VEGFR inhibitor or MET inhibitor
* Participants must not have received any anti-cancer drug (investigational or standard of care drug, except osimertinib) within 21 days prior to sub-study randomization

  * Note: osimertinib may continue up to the day prior to study treatment initiation
* Participants must not have received any radiation therapy within 14 days prior to sub-study randomization
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have had a major surgery within 14 days prior to sub-study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* Participants must not have received a live attenuated vaccination within 28 days prior to sub-study randomization. All COVID-19 vaccines that have received Food and Drug Administration (FDA) approval or FDA emergency use authorization are acceptable
* Participants must not have received strong inducers of CYP3A4 (including herbal supplements such as St. John's Wort); CYP3A4 inhibitors; CYP1A2 substrates; P-gp and BCRP substrates; sensitive substrates of MATE1 and MATE2K; or drugs that are known to prolong QT interval within 7 days prior to sub-study registration and must not be planning to use any of these throughout protocol treatment
* Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to sub-study randomization
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* 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

Primary outcomes:
measure: Investigator-assessed progression-free survival
timeFrame: From date of sub-study randomization to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Secondary outcomes:
measure: Duration of response
timeFrame: From date of first documentation of response to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a response, assessed up to 3 years
measure: Dose limiting toxicity (DLT)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cancer Center at Saint Joseph's
state: Arizona
city: Arroyo Grande
country: United States
facility: Mission Hope Medical Oncology - Arroyo Grande
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center �� Carmichael
state: California
city: Carmichael
country: United States
facility: Mercy San Juan Medical Center
state: California
city: Elk Grove
country: United States
facility: Mercy Cancer Center - Elk Grove
state: California
city: Modesto
country: United States
facility: Memorial Medical Center
state: California
city: Palo Alto
country: United States
facility: Palo Alto Medical Foundation Health Care
state: California
city: Rocklin
country: United States
facility: Mercy Cancer Center - Rocklin
state: California
city: Sacramento
country: United States
facility: Mercy Cancer Center - Sacramento
state: California
city: San Luis Obispo
country: United States
facility: Pacific Central Coast Health Center-San Luis Obispo
state: California
city: Santa Maria
country: United States
facility: Mission Hope Medical Oncology - Santa Maria
state: California
city: Sunnyvale
country: United States
facility: Palo Alto Medical Foundation-Sunnyvale
state: California
city: Woodland
country: United States
facility: Woodland Memorial Hospital
state: California
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers-Penrose
state: Colorado
city: Colorado Springs
country: United States
facility: Saint Francis Cancer Center
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Durango
country: United States
facility: Mercy Medical Center
state: Colorado
city: Durango
country: United States
facility: Southwest Oncology PC
state: Colorado
city: Lakewood
country: United States
facility: Saint Anthony Hospital
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center-Gainesville
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: Washington
country: United States
facility: Illinois CancerCare - Washington
state: Illinois
city: Council Bluffs
country: United States
facility: Alegent Health Mercy Hospital
state: Iowa
city: Bardstown
country: United States
facility: Flaget Memorial Hospital
state: Kentucky
city: Corbin
country: United States
facility: Commonwealth Cancer Center-Corbin
state: Kentucky
city: Lexington
country: United States
facility: Saint Joseph Hospital
state: Kentucky
city: Lexington
country: United States
facility: Saint Joseph Radiation Oncology Resource Center
state: Kentucky
city: Lexington
country: United States
facility: Saint Joseph Hospital East
state: Kentucky
city: London
country: United States
facility: Saint Joseph London
state: Kentucky
city: Mount Sterling
country: United States
facility: Saint Joseph Mount Sterling
state: Kentucky
city: Brewer
country: United States
facility: Lafayette Family Cancer Center-EMMC
state: Maine
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Kearney
country: United States
facility: CHI Health Good Samaritan
state: Nebraska
city: Lincoln
country: United States
facility: Saint Elizabeth Regional Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Lakeside Hospital
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Papillion
country: United States
facility: Midlands Community Hospital
state: Nebraska
city: Moorestown
country: United States
facility: Virtua Samson Cancer Center
state: New Jersey
city: Voorhees
country: United States
facility: Virtua Voorhees
state: New Jersey
city: Cincinnati
country: United States
facility: Good Samaritan Hospital - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute-Westside
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute-Anderson
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Medford
country: United States
facility: Aspirus Medford Hospital
state: Wisconsin
city: Rhinelander
country: United States
facility: Ascension Saint Mary's Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Ascension Saint Michael's Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
Study officials:
affiliation: SWOG Cancer Research Network
name: Sarah B Goldberg
role: PRINCIPAL_INVESTIGATOR
References: