A Phase II Trial of Telisotuzumab Vedotin With Osimertinib for EGFR Mutated NSCLC With c-MET Overexpression That is Progressing on Osimertinib

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 60 participants

Study Arms

• Treatment (telisotuzumab vedotin and osimertinib) (EXPERIMENTAL)
  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

• PROCEDURE: Biopsy Procedure — Undergo tumor biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• DRUG: Osimertinib — Given PO

Primary Outcomes

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

Secondary Outcomes

• 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)

Eligibility Criteria

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 ther

Trial Locations

• UCLA / Jonsson Comprehensive Cancer Center, Los Angeles, California, United States

Contact Information

• Kim Kelly — CONTACT
  Phone: 310-206-8309
  Email: KMKelly@mednet.ucla.edu
• James Chauv — CONTACT
  Phone: 310-747-7445
  Email: JChauv@mednet.ucla.edu

Study Officials

• Jonathan W Goldman, MD — PRINCIPAL_INVESTIGATOR
  UCLA / Jonsson Comprehensive Cancer Center

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