Telisotuzumab Vedotin and Osimertinib for the Treatment of Progressive, Incurable, Non Small Cell Lung Cancer
A Phase II Trial of Telisotuzumab Vedotin With Osimertinib for EGFR Mutated NSCLC With c-MET Overexpression That is Progressing on Osimertinib
2 other identifiers
interventional
60
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 6, 2026
CompletedFirst Posted
Study publicly available on registry
January 7, 2026
CompletedStudy Start
First participant enrolled
February 19, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2028
April 20, 2026
April 1, 2026
12 months
January 6, 2026
April 15, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
Up to 2 years
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.
From treatment initiation to disease progression per RECIST 1.1 criteria or death, up to 2 years
Secondary Outcomes (3)
Duration of response
From documentation of tumor response to disease progression, up to 2 years
Time to response
From treatment initiation until documentation of tumor response, up to 2 years
Overall survival
From randomization to death by any cause, up to 2 years
Study Arms (1)
Treatment (telisotuzumab vedotin and osimertinib)
EXPERIMENTALPatients receive telisotuzumab vedotin IV on days 1 and 15 of cycles 1-3 and on day 1 of subsequent cycles. Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, brain MRI, if needed, and blood sample collection throughout the study. Patients also optionally undergo tumor biopsy during follow-up.
Interventions
Undergo tumor biopsy
Undergo blood sample collection
Undergo CT scan
Undergo MRI
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +7 more criteria
You may not qualify if:
- 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
- Subjects with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for the study
- Subject must not have a history of idiopathic lung disease, drug-induced idiopathic lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, radiation pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Major surgical procedures or serious trauma within 4 weeks prior to cycle (C) 1 day (D) 1, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) do not require a washout
- The patient has any ongoing or active infection requiring the use of parenteral anti-microbial agents. Patient with a history of HIV with an undetectable viral load and a CD4 count over 200 are eligible. Patients with a history of hepatitis B or hepatitis C, an undetectable viral load, and liver function tests (LFT) testing which meets criteria for the study are eligible
- History of another cancer within 2 years of study initiation, with the exception of fully treated cancers unlikely to affect the assessment of the study treatment safety or efficacy including early-stage breast, prostate, bladder, non-melanomatous skin, thyroid, cervical, or endometrial cancer. Additionally, subjects must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization. Hormonal therapy is allowed provided that the participant otherwise meets trial criteria
- Participants must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to uncontrolled ventricular arrhythmia, myocardial infarction within 6 months, stroke within 6 months, clinically significant electrocardiogram (ECG) abnormalities, any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis, grade ≥ 2 edema or lymphedema, grade ≥ 2 ascites or pleural effusion, grade ≥ 2 neuropathy, grade ≥ 2 corneal disorder as assessed by a baseline ophthalmic exam, or any psychiatric disorder that prohibits obtaining informed consent
- Patient unwilling or unable to comply with the protocol
- Any condition that, in the opinion of the investigator or sponsor-investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jonsson Comprehensive Cancer Centerlead
- AbbViecollaborator
Study Sites (1)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan W Goldman, MD
UCLA / Jonsson Comprehensive Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 6, 2026
First Posted
January 7, 2026
Study Start
February 19, 2026
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
February 1, 2028
Last Updated
April 20, 2026
Record last verified: 2026-04