Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)

Stage IV Lung Cancer AJCC v8 Clinical 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05642572
• Other study ID #: S1900G
• Secondary ID: NCI-2022-09254S1
• Status: Recruiting
• Phase: Phase 2
• Start date: May 5, 2023
• Est. completion date: May 31, 2027

Study information

• Verified date: June 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood samples

Drug:
• Capmatinib
Given PO

Procedure:
• Computed Tomography
Undergo CT scan
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Osimertinib
Given PO

Biological:
• Ramucirumab
Given IV

Locations

Country	Name	City	State
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Mercy Cancer Center ?? Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Memorial Medical Center	Modesto	California
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Woodland Memorial Hospital	Woodland	California

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-assessed progression-free survival	Will be estimated using the method of Kaplan-Meier. Medians and their associated 95% confidence intervals will be estimated using the Brookmeyer-Crowley method. Binary proportions and the associated confidence interval will be estimated.	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	Duration of response	Will be estimated using the method of Kaplan-Meier. Medians and their associated 95% confidence intervals will be estimated using the Brookmeyer-Crowley method. Binary proportions and the associated confidence interval will be estimated.	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
Secondary	Dose limiting toxicity (DLT)	Treatment-related Grade 3 or higher non hematologic toxicity, treatment-related Grade 4 or higher hematologic toxicity, or any grade of treatment-related toxicity that leads to drug discontinuation. The DLT assessment period is the first cycle of treatment. Treatment related is defined as an attribution of possible, probably, or likely related to treatment. Toxicities to be graded based on Common Terminology Criteria for Adverse Events.	Up to 3 years