Telisotuzumab Vedotin and Osimertinib for the Treatment of Progressive, Incurable, Non Small Cell Lung Cancer

Inclusion Criteria: * Male or female ≥ 18 years of age and willing and able to provide informed consent * Cytologically or histologically confirmed non small cell lung cancer (NSCLC), which is incurable with an activating and sensitizing EGFR mutation (e.g., exon 20 insertion mutations are excluded). Enrollment of patients with mutations other than exon 19 deletion and the L858R point mutation require literature supporting sensitivity to osimertinib. T790M mutations and identified EGFR mutations that are known to confer resistance to osimertinib (for instance C797S) are allowed * Predominantly adenocarcinoma histology. (Small cell or predominantly squamous cell or sarcomatoid/pleiomorphic histologies are excluded.) * Progressed on osimertinib. Osimertinib must have been included in the last systemic therapy prior to trial enrollment and the patient must be considered appropriate for continuation of osimertinib at 80 mg daily per the treating investigator * From a tumor specimen obtained following progression on osimertinib or within 4 months of study entry (as long as the specimen was obtained after osimertinib was started), subjects must have c-MET overexpressing NSCLC as assessed by a Certified Laboratory Improvement Amendments (CLIA)-certified laboratory using the VENTANA MET (SP44) RxDx assay, with intermediate or high expression, defined as either ≥ 25% and \< 50% (intermediate) or ≥ 50% (high). If local results are unavailable, central testing may be performed * Measurable disease, as per RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Able to swallow the oral study drug, has no known intolerance of study drugs or excipients, and able to comply with study requirements * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L * Platelets ≥ 100 × 10\^9/L * Hemoglobin ≥ 9 g/dL * Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated\* creatinine clearance ≥ 50 mL/min (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) * Creatinine clearance may be calculated using a 24 hour urine collection, by the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) per the Modification of Diet in Renal Disease (MDRD) GFR equation * Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver metastases * Albumin ≥ 3.0 g/dL * Female participants of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum test must be negative for pregnancy for the participant to be eligible. Female participants must agree to use a highly effective method of contraception from the beginning of screening until 7 months after the last dose of the telisotuzumab vedotin, or be of nonchildbearing potential.Nonchildbearing potential is defined as follows (by other than medical reasons): * ≥ 45 years of age and has not had menses for \> 2 years, in the absence of conditions that could lead to amenorrhea (i.e., post chemotherapy), * Participants who have been amenorrhoeic for \< 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation, or * Surgical sterilization (Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation) * Male patients having sex with a female partner of childbearing potential or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 4 months after the last dose of telisotuzumab vedotin * Male and female participants must agree not to donate sperm or eggs, respectively starting from the first study-drug treatment, Men must not donate sperm during trial therapy and for 4 months after receiving the last dose of study medication and women must not donate eggs during trial treatment and for 7 months after receiving the last dose of study medication Exclusion Criteria: * Concurrent enrollment in another clinical study, unless enrolled only in the follow-up period or an observational study * Prior c-MET targeted antibody drug conjugate with a microtubule toxin (such as monomethylauristatin E \[MMAE\]). Prior MET antibody without a toxin, prior MET antibody drug conjugate (ADC) with a non-microtubule, and prior MET TKI therapy are acceptable * Any chemotherapy, immunotherapy, biologic, hormonal therapy, or investigational systemic therapy for cancer treatment in the prior 3 weeks or within 5 half-lives of the medication, whichever is shorter. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable * Thoracic radiation of ≥ 30 grey (Gy) within 6 months. Other radiation within 2 weeks with the exception: Stereotactic, palliative radiation for bone metastases is acceptable without a washout as long as no lung parenchyma was included in the radiation field * Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded * Has not recovered (recovery is defined as National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events \[CTCAE v 5.0\] grade ≤ 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion. Other grade 2 or less toxicities not constituting a safety risk based on the investigator's judgment are acceptable. * Subjects with hormone deficiencies caused by prior antican