Recruiting
Phase 2

Telisotuzumab Vedotin & Osimertinib

Sponsor:

Jonsson Comprehensive Cancer Center

Code:

NCT07323641

Conditions

Lung Non-Small Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Osimertinib

Study Details

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.

Conditions

Lung Non-Small Cell Carcinoma

Study ID

NCT07323641

Start date

Feb 19, 2026

Status verified date

Apr, 2026

Completion date

Feb 1, 2028

Anticipated

Primary completion date

Feb 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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

Study Design

Enrollment

60 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (telisotuzumab vedotin and osimertinib)

Patients 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

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT scan

Magnetic Resonance Imaging

Undergo MRI

Osimertinib

Given PO

Survey Administration

Ancillary studies

Telisotuzumab Vedotin

Given IV

Primary outcome measure

  • Objective response rate (ORR) [ Time Frame: Up to 2 years ]
  • Progression free survival (PFS) [ Time Frame: From treatment initiation to disease progression per RECIST 1.1 criteria or death, up to 2 years ]

Central Contacts and Locations

Central contacts

Kim Kelly

310-206-8309KMKelly@mednet.ucla.edu

James Chauv

310-747-7445JChauv@mednet.ucla.edu

Locations

UCLA / Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

James Chaov

310-747-7445JChauv@mednet.ucla.edu

Kim Kelly

310-206-8309kmkelly@mednet.ucla.edu

Principal Investigator:

Jonathan W. Goldman, MD

More Information

Sponsor

Jonsson Comprehensive Cancer Center

Last update posted

Apr 20, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Jonsson Comprehensive Cancer Center on 2026-04-20.