This phase II trial tests how well telisotuzumab vedotin and osimertinib works for the treatment of non small cell lung cancer that is growing, spreading, or getting worse (progressive) and for which no treatment is currently available (incurable). Telisotuzumab vedotin is a monoclonal antibody, called telisotuzumab, linked to a toxic agent, called vedotin. Telisotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as c-Met receptors, and delivers vedotin to kill them. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving telisotuzumab vedotin and osimertinib may be effective for treating progressive, incurable non small cell lung cancer.
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
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
Single group
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Osimertinib
DrugGiven PO
Survey Administration
Other interventionAncillary studies
Telisotuzumab Vedotin
Biological/VaccineGiven IV
Objective response rate (ORR)
Defined as complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The ORR estimate and its associated 95% confidence interval (CI) will be calculated.
Progression free survival (PFS)
The Kaplan-Meier curve and its 95% CI will be used to infer the PFS. The median time PFS will be compared to median survival time of 4.2 months base on historic controls, using Brookmeyer-Crowley method.
Duration of response
The Kaplan-Meier curve and its 95% CI will be used to infer the endpoint.
Time to response
The Kaplan-Meier curve and its 95% CI will be used to infer the endpoint.
Overall survival
The Kaplan-Meier curve and its 95% CI will be used to infer the endpoint.
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Jonsson Comprehensive Cancer Center
Lead sponsor
AbbVie
Collaborator
