A Phase 3 Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Versus Docetaxel in Subjects with Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer

• Subject must have c-Met overexpressing NSCLC as assessed by an AbbVie
designated IHC laboratory using the VENTANA MET (SP44) RxDx assay.
• Archival or fresh tumor material must be submitted for assessment of c-Met
levels by an AbbVie designated IHC laboratory during the Pre-Screening period.
Tumor material from the primary tumor site and/or metastatic sites are allowed.
If archival tissue is negative for c-Met overexpression, fresh biopsy material
may be submitted for reassessment of c-Met expression. - If a participant was
prescreened for Study M14-239 but did not enroll, tumor material previously
submitted for Study M14-239 may be used for Study M18-868 Pre-Screening upon
confirmation from AbbVie that sufficient evaluable tumor material is available
(Except China).
• Subject has adequate bone marrow, renal, and hepatic function
• Subject must have histologically documented non-squamous cell NSCLC that is
locally advanced or metastatic.
• Subjects must have a known EGFR activating mutation status.
-Subjects with actionable EGFR activating mutations are not eligible.
• Subjects with actionable alterations in genes other than EGFR are eligible.
• Subject must have measurable disease per RECIST version 1.1.
• Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance
Status of 0 to 1.
• Subject must have received no more than 1 line of prior systemic cytotoxic
chemotherapy in the locally advanced or metastatic setting.
-Neoadjuvant and adjuvant systemic cytotoxic chemotherapy would count as a
prior line for eligibility purposes if progression occurred within 6 months of
the end of therapy.
• Subject must have progressed on at least 1 line of prior therapy for locally
advanced/metastatic NSCLC:
- Subjects WITHOUT an actionable gene alteration: subjects must have
progressed on (or be considered ineligible for) platinum-based chemotherapy
and immune checkpoint inhibitor (as monotherapy or in combination with
chemotherapy).
- Subjects WITH an actionable gene alteration for which immune checkpoint
inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase
[ALK] translocation): subjects must have progressed on (or be considered
ineligible for) anti-cancer therapy targeting driver gene alterations and
platinum-based chemotherapy.
- Subjects with actionable gene alterations for which immune checkpoint
inhibitor is standard of care must have also progressed on (or be considered
ineligible for) immune checkpoint inhibitor (as monotherapy or in combination
with chemotherapy).
• Subject must be considered appropriate for docetaxel therapy based on the
assessment of the treating physician.
• No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection,
the subject must have a negative molecular (e.g., polymerase chain reaction
[PCR]) test or 2 negative antigen test results at least 24 hours apart. In
addition, if based on the answers to the SARS-CoV-2 Infection Risk Assessment
Tool the site considers the subject currently at risk for developing SARS-CoV-2
infection, then the subject should either be tested or advised to come back for
study screening after 14 days. Subject must not have had any serious SARS-CoV-2
infection that required mechanical ventilation/endotracheal intubation or
extracorporeal membrane oxygenation (ECMO) support in the past 6 months, or
long-term complications from SARS-CoV-2 infection that are not resolved at the
time of prescreening.
• Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be
screen failed and may only rescreen for the study after they meet the
SARS-CoV-2 infection viral clearance criteria listed in the protocol.

• Subject has adenosquamous histology.
• Subject has received prior c-Met-targeted antibodies, prior telisotuzumab
vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting
of monomethylauristatin E.
• Subject has received prior docetaxel therapy.
• Subjects with metastases to the central nervous system (CNS) are eligible
only after definitive therapy (such as surgery or radiotherapy) is provided and:
- There is no evidence of progression of CNS metastases at least 2 weeks after
definitive therapy.
- They are asymptomatic and off or on a stable or reducing dose of systemic
steroids and/or anticonvulsants for at least 2 weeks prior to first dose of
telisotuzumab vedotin.
• Subjects with a history of other malignancies except:
- Malignancy treated with curative intent and with no known active disease
present for >= 2 years before the first dose of study drug and felt to be at low
risk for recurrence by investigator.
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease.
- Adequately treated carcinoma in situ without current evidence of disease.
• Subject with a 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 CT scan.
• History of prior radiation pneumonitis in the radiation field (fibrosis) is
permitted.
• Subject with unresolved AE >= Grade 2 from prior anticancer therapy, except
for alopecia or anemia.
• Subject has had major surgery within 21 days prior to the first dose of
telisotuzumab vedotin.
• Subjects with the following:
- Known human immunodeficiency virus (HIV) infection. Note: HIV testing is
not required for eligibility for this protocol unless mandated by local
regulatory authority or ethics committee/institutional review board.
- Active hepatitis B virus (HBV) infection, defined by HBV DNA >= 500 IU/mL or
hepatitis B surface antigen (HBsAG) positivity associated with HBV DNA >= 500
IU/mL. In subjects with known HBV infection, the presence of active infection
must be tested locally. If HBV status is unknown, it must be tested locally at
screening if required by local regulatory authority or ethics
committee/institutional review board.
- Active hepatitis C virus (HCV) infection, defined by HCV RNA positivity.
Subjects cured of HCV infection may be included in the study. In subjects with
known HCV infection, the presence of active infection must be tested locally.
If HCV status is unknown, it must be tested locally at screening if required by
local regulatory authority or ethics committee/institutional review board.
- Uncontrolled autoimmune disease.
• Subject has clinically significant condition(s) including but not limited to
the following:
- Clinically significant vascular disease, including:
- Myocardial infarction within 1 year or stroke within 6 months prior to first
dose of study drug, or unstable or uncontrolled disease/condition related to or
affecting cardiac function (e.g., unstable angina, congestive heart failure,
New York Heart Association Class III-IV), cardiac arrhythmia (CTCAE Version 5
Grade 2 or higher), or clinically
significant electrocardiogram (ECG) abnormalities.
- Screening 12-lead ECG showing a baseline QT interval as corrected by
Fridericia's formula (QTcF) > 470 msec.
- 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
• Subject has a history of major immunologic reaction to any immunoglobulin G
(IgG)-containing agent. Subject has hypersensitivity to docetaxel or
polysorbate 80.
• Subjects have received any live vaccine within 30 days of the first dose of
study drug.
• Treatment with any of the following therapies within the noted time intervals
prior to the first dose of telisotuzumab vedotin:
- Within 1 week (7 days): herbal therapy or strong cytochrome P450 3A4 (CYP3A4)
inhibitors.
- Within 2 weeks (14 days): small molecule targeted agents with half-life <
7 days; radiation not involving the lungs.
- Within 4 weeks (28 days) or 5 half-lives (whichever is shorter): systemic
cytotoxic chemotherapy; small molecule targeted agents with half-life >= 7 days;
monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or
T-cell or other cell-based therapies.
• Subjects must not have had radiation therapy to the lung within 6 months
prior to the first dose of study drug and until study drug is permanently
discontinued.