A Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Vedotin (ABBV-399) Moves Through the Body as a Monotherapy in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Brief Summary
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-small cell lung cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to assess how safe telisotuzumab vedotin is in adult participants with NSCLC. Change in disease activity and adverse events will be assessed.

Telisotuzumab vedotin is an investigational drug being developed for the treatment of NSCLC. Participants will be randomly assigned a treatment of telisotuzumab vedotin in 1 of 3 arms at an 1:1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin at different doses. Approximately 150 adult participants with c-Met overexpressing NSCLC will be enrolled in the study at approximately 70 to 80 sites worldwide.

Participants will receive IV telisotuzumab vedotin at 1 of 3 dose regimens as part of a 3 year study duration.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Brief Title
A Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Vedotin (ABBV-399) Moves Through the Body as a Monotherapy in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Central Contacts
Central Contact Role
Contact
Central Contact Phone
844-663-3742
Central Contact Email
abbvieclinicaltrials@abbvie.com
Completion Date
Completion Date Type
Estimated
Conditions
Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:

* Projected life expectancy of at least 12 weeks.
* Must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory
* Must have histologically or cytologically documented NSCLC that is locally advanced or metastatic.
* Must have a known epidermal growth factor receptor (EGFR) activating mutation status.
* Actionable alterations in genes other than EGFR are permitted.
* Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Must have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting, as stated in the protocol.
* Must have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC, as stated in the protocol.

Exclusion Criteria:

* Adenosquamous or neuroendocrine histology, or sarcomatoid features.
* Actionable EGFR activating mutations.
* Received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E.
* Received prior docetaxel therapy.
* Metastases to the central nervous system (CNS). Participants with CNS metastases are eligible only after adequate treatment (such as surgery or, radiotherapy, or drug therapy) is provided, as stated on the protocol.
* History of other malignancies except those stated in the protocol.
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan, as noted in the protocol.
* Unresolved clinically significant adverse event (AE) \>= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Participants with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
* Major surgery within 21 days prior to randomization.
* Clinically significant condition(s) including but not limited to those listed in the protocol.
* 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.
* Active uncontrolled bacterial or viral infection.
* Active corneal disorder.
Inclusion Criteria
Inclusion Criteria:

* Projected life expectancy of at least 12 weeks.
* Must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory
* Must have histologically or cytologically documented NSCLC that is locally advanced or metastatic.
* Must have a known epidermal growth factor receptor (EGFR) activating mutation status.
* Actionable alterations in genes other than EGFR are permitted.
* Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Must have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting, as stated in the protocol.
* Must have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC, as stated in the protocol.

Gender
All
Gender Based
false
Keywords
Non-Small Cell Lung Cancer
NSCLC
Telisotuzumab Vedotin
ABBV-399
TeliMET NSCLC-04
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06568939
Org Class
Industry
Org Full Name
AbbVie
Org Study Id
M25-274
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2, Open-Label, Randomized, Global Study of Three Telisotuzumab Vedotin Regimens in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer
Primary Outcomes
Outcome Description
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Outcome Measure
Percentage of Participants with Treatment-Emergent Adverse Events (AE)s (Any-grade and Grade >= 2)
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
ILD is defined by ILD standardized MedDRA query (SMQ) (broad) per investigator and determined per adjudication (any-grade and Grade \>= 2).
Outcome Measure
Percentage of Participants with Treatment-Emergent Interstitial Lung Disease (ILD)
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
Peripheral neuropathy is defined by peripheral neuropathy SMQ (narrow) (any-grade and Grade \>= 2)
Outcome Measure
Percentage of Participants with Treatment-Emergent Peripheral Neuropathy
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
Treatment-emergent ocular surface disorders defined by corneal epitheliopathy company MedDRA query (CMQ) (any-grade and Grade \>= 2).
Outcome Measure
Percentage of Participants with Treatment-Emergent Ocular Surface Disorders
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Outcome Measure
Percentage of Participants with Treatment-Emergent AEs Leading to Study Drug Discontinuation
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Outcome Measure
Percentage of Participants with Grade 5 Treatment-Emergent AEs
Outcome Time Frame
Up to Approximately 3 Years
Outcome Description
OR will be defined as achieving confirmed complete response (CR) or confirmed partial response (PR) based on response evaluation criteria in solid tumors (RECIST), version 1.1.
Outcome Measure
Objective Response (OR) by Blinded Independent Central Review (BICR)
Outcome Time Frame
Up to Approximately 3 Years
Secondary Outcomes
Outcome Description
Concentrations of telisotuzumab vedotin conjugate in serum.
Outcome Time Frame
Up to 26 Weeks
Outcome Measure
Concentrations of Telisotuzumab Vedotin Conjugate in Serum
Outcome Description
Concentrations of MMAE payload in plasma.
Outcome Time Frame
Up to 26 Weeks
Outcome Measure
Concentrations of Monomethylauristatin E (MMAE) Payload in Plasma
Outcome Description
Percentage of participants with ADAs of telisotuzumab vedotin.
Outcome Time Frame
Up to 26 Weeks
Outcome Measure
Percentage of Participants with Antidrug Antibodies (ADAs) of Telisotuzumab Vedotin
Outcome Description
Percentage of participants with nADAs of telisotuzumab vedotin.
Outcome Time Frame
Up to 26 Weeks
Outcome Measure
Percentage of Participants with Neutralizing Antidrug Antibodies (nADAs) of Telisotuzumab Vedotin
Outcome Description
The PRO-CTCAE is a patient-reported outcome measurement system developed to assess symptomatic toxicity in patients participating in cancer clinical trials. PRO-CTCAE includes 124 items representing 78 symptomatic toxicities drawn from the Common Terminology Criteria for Adverse Events (CTCAE). PRO-CTCAE items evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. All questions employ a 7-day recall period and are scored from 0 to 4 (or 0/1 for absent/present).
Outcome Time Frame
Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years
Outcome Measure
Change in Selected items of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Outcome Description
The GP5 item ("I am bothered by side effects of treatment") of FACT-G is used to assess overall treatment tolerability in patients by assessing the overall side effect impact on participants.
Outcome Time Frame
Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years
Outcome Measure
Change in GP5 item of the Functional Assessment of Cancer Therapy-General (FACT-G)
Outcome Description
DoR is defined for confirmed responders as the time from the participants' initial response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause.
Outcome Time Frame
Up to Approximately 3 Years
Outcome Measure
Duration of Response (DoR) by BICR
Outcome Description
PFS will be defined as the time from randomization to the first occurrence of radiographic progression based on RECIST version 1.1 or death from any cause.
Outcome Time Frame
Up to Approximately 3 Years
Outcome Measure
Progression-Free Survival (PFS) by BICR
Outcome Description
OS will be defined as the time from randomization to death from any cause.
Outcome Time Frame
Up to Approximately 3 Years
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Please Specify
Study Division
Please Specify
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
TELISOTUZUMAB VEDOTIN