a study to evaluate the impact of management strategies on gastrointestinal-related adverse events in participants with non-small cell lung cancer harboring epidermal growth factor receptor (egfr) exon 20 insertion mutations receiving tak-788

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Summary: the purpose of the study is to characterize the incidence and severity of tak-788-associated diarrhea in previously treated participants with locally advanced or metastatic non-small-cell lung cancer (nsclc) whose tumors harbor egfr exon 20 insertion mutations treated with tak-788 when administered with or without intensive loperamide prophylaxis.

the drug being tested in this study is called tak-788. tak-788 administered with or without antidiarrheal prophylaxis is being tested to evaluate the impact of management strategies on gastrointestinal-related adverse events in participants with non-small cell lung cancer harboring egfr exon 20 insertion mutations receiving tak-788. the study will enroll approximately 90 patients. participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups- * cohort 1 * cohort 2 all participants will be asked to take tak-788 capsules with or without a low-fat meal in cohort 1 and tak-788 capsule with antidiarrheal prophylaxis and with or without a low-fat meal in cohort 2. this is a multi-center trial and will be conducted worldwide. the overall time to participate in this study is approximately 2 years. participants will make multiple visits to the clinic after receiving their last dose of drug for a follow-up assessment.

Eligibility criteria:
inclusion criteria: 1. diagnosed with histologically or cytologically confirmed nonsquamous cell locally advanced (not suitable for definitive therapy) or metastatic non-small-cell lung cancer (nsclc) (stage iiib or iv) nsclc; and, has received at least 1 prior line of therapy for this disease. 2. a documented epidermal growth factor receptor (egfr) mutation with in-frame exon 20 insertion, confirmed as follows: * for sites located in the united states (us): assessment must be done by a certified laboratory functioning under the guidelines of the clinical laboratory improvements amendment (clia). * for site located outside of the us: assessment must be done by an accredited local laboratory. note: a documented egfr in-frame exon 20 insertion or insertion-duplication includes but is not limited to one of the following: * a763_y764insfqea, * v769_d770insasv (also referred to as asv duplication) * d770_n771insnpg * d770_n771inssvd (also referred to as svd duplication) * h773_v774insnph (also referred to as nph duplication), or * any other in-frame insertion mutation in the exon 20 \[amino acids 739 -823\]. the egfr exon 20 insertion mutation can be either alone or in combination with other egfr or her2 mutations. the reported insertion-duplication can have been detected on either tissue or liquid biopsy using a well-validated test based on either polymerase chain reaction, sequencing or next-generation sequencing (ngs). 3. eastern cooperative oncology group (ecog) performance status of 0 to 1. 4. minimum life expectancy of ≥3 months. 5. all toxicities from prior therapy have been resolved to ≤grade 1, according to the national cancer institute common terminology criteria for adverse events (nci ctcae) v5.0 or have resolved to baseline, at the time of first dose of tak-788. exclusion criteria: 1. has been diagnosed with another primary malignancy other than nsclc, except for the following: 1. adequately treated non-melanoma skin cancer or cervical cancer in situ. 2. definitively treated non-metastatic prostate cancer. 3. non-nsclc primary malignancies that are definitively relapse-free for ≥3 years. 2. has unstable brain metastases to include previously untreated intracranial central nervous system (cns) metastases or previously treated intracranial cns metastases with radiologically documented new or progressing cns lesions. - brain metastases that are stable do not preclude eligibility if they have been treated with surgery and/or radiation, and have been stable without requiring corticosteroids to control symptoms within 7 days before randomization, and have no evidence of new or enlarging brain metastases. 3. has a current spinal cord compression (symptomatic or asymptomatic that is detectable by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic). 4. currently has or has had a history of interstitial lung disease, to include radiation or drug related pneumonitis that requires/required steroid treatment. 5. has an ongoing or active infection, to include but not limited to infections requiring intravenous antibiotics or has a known history of hiv. testing for hiv is not required in the absence of history. note: hepatitis b surface antigen-positive participants are allowed to enroll if hepatitis b virus (hbv) deoxyribonucleic acid (dna) is below 1000 copies/ml in the plasma. patients who are positive for anti-hepatitis c virus antibody can be enrolled but must not have detectable hepatitis c virus (hcv) rna in the plasma. 6. have uncontrolled hypertension. participants with hypertension should be under treatment on study entry to control blood pressure. 7. a prolonged qtcf interval, or is being treated with medications known to be associated with the development of torsades de pointes. 8. has a gi illness or disorder, including but not limited to a history of gi perforation, that could affect oral absorption of tak-788.

Keywords: drug therapy