For US Residents only
The EXCLAIM-2 Clinical Study is an investigational study testing the safety and effectiveness of an investigational medication versus platinum-based chemotherapy for patients with non-small cell lung cancer (NSCLC) with tumors that are positive for an EGFR exon 20 insertion mutation who have not yet been treated.
NSCLC is the most common form of lung cancer, accounting for approximately 80-85% of all lung cancers. There are a number of different genetic mutations associated with NSCLC – making it complex to study, diagnose and treat. 1-2 One of these is a mutation in the epidermal growth factor receptor (EGFR) gene.
EGFR mutations are found in approximately 15-40% of patients with NSCLC, with increased frequency in Asian patients.1-3 Testing positive for the EGFR mutation means that the EGFR protein that’s normally present on the surface of lung cells is mutated or damaged, making it an abnormal protein. The abnormal EGFR protein performs irregularly, causing uncontrollable cell growth that can lead to cancer.4
Exon 20 insertion mutations are different from other EGFR mutations. This mutation occurs in a specific region of the EGFR protein called exon 20. Insertions are extra amino acids (proteins are made up of amino acids) that are added to the EGFR protein and cause irregular function.4
In the United States, EGFR exon 20 mutations occur in approximately 2.5-9% of all EGFR mutations in NSCLC.5,6 Therefore, patients with NSCLC who have EGFR exon 20 insertion mutations make up a small proportion of the NSCLC population, and there are currently no targeted therapy options to treat them, as approved EGFR tyrosine kinase inhibitors were not designed for patients with this subtype of EGFR mutations. Targeted therapies are a type of investigational medication that blocks the growth and spread of cancer cells by targeting specific genes, proteins, or the tissue environment that contributes to the growth, progression and survival of cancer. (see https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet) The EXCLAIM-2 Clinical Study is investigating a potential medication for treating NSCLC patients who have not received prior treatment and whose tumors show an abnormal EGFR protein with an EGFR exon 20 insertion mutation.
If you don’t know your or your loved one’s specific mutation status, talk to your doctor about genetic testing, or if you have been diagnosed with an EGFR mutation, ask your doctor if it’s specifically an EGFR exon 20 insertion mutation. Getting tested is required in order for your doctor to help you determine if this study might be right for you or your loved one.
1. American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed August 2019. 2. Kris MG, et al. JAMA, 2014;311:1998-2006. Accessed October 2019. 3. Kohno T, Nakaoku T, Tsuta K, et al. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015;4(2):156-164. 4. Vanderbilt University Medical Center. Lung Cancer and EGFR Exon 20 Insertion Mutations. https://mc.vanderbilt.edu/ckm/gl/mutation_profiles/pdfopen.php?fnp=lung_cancer/content/EGFR Lung_Cancer_and_EGFR_Exon_20_ Insertions.pdf. March 2016. Accessed July 26, 2019. 5. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. 6. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229.
Please speak with your doctor if you’re unsure about your or your loved one’s specific mutation status. (If you are filling this out on behalf of the patient, please answer based on the patient’s information.)
Unfortunately, at this time you haven’t met the eligibility requirements to enroll in the EXCLAIM-2 Clinical Study. If you’ve never tested for an EGFR exon 20 insertion mutation, it’s a requirement in order to be eligible. Ask your doctor about getting tested. Please use the Doctor Discussion Guide below to talk to your doctor about your options and to find out whether additional genetic testing is appropriate.
Download Doctor Discussion Guide
Lashell Robinson, Takeda's Director of Diversity and Inclusion in Clinical Trials
Challenges and importance of inclusive research
Dr. Danny Nguyen, an EXCLAIM-2 Study Principal Investigator
NSCLC EGFR EXON-20 research
Types of EGFR testing that capture the most mutations
How to access low-cost solutions for your patients
Dr. Florin Vranceanu, Takeda Medical Director
EXCLAIM-2 Study* (Mobocertinib/Exkivity)
TAK-788/ Mobocertinib/Exkivity, FDA approved therapy for NSCLC targeting EGFR EXON-20 mutations
How Takeda is supporting patients
How to refer potential patients
*This is not a complete list of eligibility criteria.
Before making a decision regarding study enrollment, please consult the complete list here.
Male or female participants who are at least 18 years old
Have not received previous treatment for locally advanced or metastatic NSCLC
Must have measurable disease by response evaluation criteria in solid tumors (RECIST v1.1)
Tested positive for EGFR exon 20 insertion mutation and sufficient tumor tissue available for central analysis
Adequate organ function at baseline
Minimum life expectancy of 3 months or more
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of less than or equal to (≤) 450 milliseconds (ms) in males or ≤470 ms in females
Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days prior to the first dose of the study
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Oncogenic driver mutations, including EGFR mutations, are known to cause approximately 50% of NSCLC cases.1,2 Specifically, EGFR mutations are expressed in 15-40% of patients with advanced NSCLC.2,3
A more rare mutation, the EGFR exon 20 insertion, occurs in 2.5-9% of all EGFR mutations and these patients do not tend to respond to current EGFR tyrosine kinase inhibitors.4,5 Finding out about their exon 20 status through genetic testing may help determine whether they qualify for the EXCLAIM-2 Clinical Study evaluating the safety and efficacy an investigational tyrosine kinase inhibitor (TKI) for patients with NSCLC whose tumors have an EGFR exon 20 insertion mutation who have not yet received prior treatment.
For your patients who have not received prior treatment and have not been tested for EGFR or have tested positive for EGFR, additional genetic testing can help confirm their exon 20 status. Ordering a test (preferably a Next-Generation Sequencing, [NGS], test) can help determine whether this study may be right for them.6,7
NGS testing is preferred since it finds all the exon 20 insertion variants. PCR testing is another alternative, however, PCR does not detect all variants of exon 20 insertions using tumor DNA.8
The EXCLAIM-2 Clinical Study is a Phase 3, open-label, multicenter, active-comparator, international study that plans to evaluate the safety and efficacy of an investigational tyrosine kinase inhibitor (TKI) as a first-line treatment versus platinum-based chemotherapy in approximately 318 patients with locally advanced or metastatic NSCLC whose tumors express EGFR exon 20 insertions. Participants will be administered the experimental medication at 160 mg once daily or chemotherapy intravenously.
The full inclusion criteria for the EXCLAIM-2 Clinical Study are available here.
Genetic testing can help identify abnormal changes in your patients’ genes. Genetic tests, like NGS, analyze DNA to detect mutations that could lead to cancer.8,9
Targeted therapies differ from traditional chemotherapy and treat cancer by being able to target specific gene changes. These therapies can block the process that tells cancer cells to grow and divide or destroy cancer cells.10
Learn more about targeted therapies here.
NGS is a single test that determines the genetic sequence of multiple genomic targets. It also has the advantage to detect mutations that may be present at low levels in tumors. Detecting these mutations is generally difficult but critical in hematological and solid tumor malignancies. Typically, NGS provides you with a comprehensive genomic profile that could be used to help guide your investigational medication selection process.7,8
Order an NGS test that includes the ability to detect EGFR exon 20 for your patients, and see if they’re eligible for the EXCLAIM-2 Clinical Study.
PCR is a different testing technique that copies small segments of DNA in order to effectively conduct a genetic analysis. Different PCR tests can be used to detect insertions by identifying any mutation that differs from a normal sequence. However, PCR testing is currently limited to detecting a certain number of genes and genetic mutations. This can make it difficult to detect all the different types of EGFR exon 20 insertion mutations. This is why NGS is preferred.7,8,11
Learn more about the guidelines associated with genetic testing for NSCLC here.
1. Crossland V, Li S, Galaznik A. The Frequency and Spectrum of EGFR Exon 20 Insertions in NSCLC: A Global Literature Review. 2. Kris M, Johnson B, Berry L, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 3. Kohno T, Nakaoku T, Tsuta K, et al. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015;4(2):156-164. 4. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. 5. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Non-Small Cell Lung Cancer (Version 5.2019). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed July 26, 2019. 7. Cancer Genetic Incorporated. Access the Next-Generation of Cancer Diagnostics. https://www.cancergenetics.com/laboratory-services/specialty-tests/focus-ngs/focus-overview/. Accessed July 26, 2019. 8. My Cancer Genome. Types of Molecular Tumor Testing. https://www.mycancergenome.org/content/page/molecular-testing/. Accessed July 26, 2019. 9. NIH U.S. National Library of Medicine. What is genetic testing? https://ghr.nlm.nih.gov/primer/testing/genetictesting. July 16, 2019. Accessed July 26, 2019. 10. Cancer.net. Understanding Targeted Therapy. https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-targeted-therapy. January 1, 2019. Accessed July 26, 2019. 11. National Human Genome Research Institute. What is PCR? https://www.genome.gov/about-genomics/fact-sheets/Polymerase-Chain-Reaction-Fact-Sheet. Accessed July 26, 2019.