Inclusion Criteria:

• Subjects or their legally authorized representative must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB) / Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures. Where confirmed as a local requirement, the subject (not a representative) must provide the written consent.
• Adult male or female, at least 18 years old.
• Subjects must have c-Met+ NSCLC as assessed by an AbbVie designated IHC laboratory. Subject must submit archival or fresh tumor material for assessment of c-Met levels during the pre-screening period. If archival tissue is c-Met negative, fresh biopsy material may be submitted for reassessment of c-Met ecpression.
• If a subject meets eligibility criteria for c-Met protein expression level based on archival tissue material, subject must agree to submit fresh tumor material for assessment of c-Met protein expression level prior to first dose of telisotuzumab vedotin.
• Subjects have adequate bone marrow, renal, and hepatic function as follows:
  • Bone marrow: Absolute neutrophil count (ANC) ≥ 1,000/mm^3;
  • Platelets ≥ 100,000/mm^3 ; Hemoglobin ≥ 9.0 g/dL;
  • Renal function: Serum creatinine ≤ 1.5 × the Institution's Upper Limit of Normal (ULN) range or creatinine clearance ≥ 50 mL/min measured by 24-hour urine or estimated by the Cockcroft-Gault formula: CrCl (mL/min) = (140 – age in years) × (weight in kg) (× 0.85 if female) 72 × serum creatinine (mg/dL);
  • Hepatic function: Bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN, and albumin ≥ 3.0 g/dL;
  • Hepatic function for subjects with liver metastases: bilirubin ≤ 1.5 × ULN, AST, ALT, and GGT ≤ 5.0 × ULN, and albumin ≥ 3.0 g/dL.
• Subjects are willing and able to comply with procedures required in this protocol.
• Subjects with histologically documented non-squamous NSCLC with known EGFR status (wild type or mutant; with site documented status). Of note, subjects with other actionable mutations are eligible as long as EGFR status is known and all other eligibility criteria are met.
• Subjects must have locally advanced or metastatic NSCLC.
• Subjects have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Subjects must have measurable disease per RECIST version 1.1.
• Subjects must not have adenosquamous histology.
• Subjects must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.
  • Multiple lines of TKIs targeting the same TK count as 1 line of therapy for the purposes of this eligibility criterion.
• Subjects must have progressed on systemic cytotoxic chemotherapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible for an immune checkpoint inhibitor), and prior anti-cancer therapies targeting driver gene alterations (if applicable).
• Subjects should not have received prior c-Met-targeted antibody-based therapies.
• 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 4 weeks after definitive therapy.
  • They are asymptomatic and off or on stable or reducing dose of systemic steroids and/or anticonvulsants for at least 2 weeks prior to first dose of telisotuzumab vedotin.
• Subjects must not have 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.
• Subjects must not have a history of interstitial lung disease or pneumonitis that required treatment with systemic steroids.
• Subjects must not have any evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or interstitial lung disease within 3 months of the planned first dose of the study drug.
• Subjects must not have unresolved clinically significant adverse events Grade ≥ 2 from prior anticancer therapy, except for alopecia or anemia.
• Subjects must not have had major surgery within 21 days prior to the first dose of telisotuzumab vedotin.
• Subjects must not have received radiation therapy to the lung < 6 months prior to the first dose of telisotuzumab vedotin.
• Subjects must not have a clinically significant condition(s) including, but not limited to, the following:
  • Grade ≥ 2 edema or lymphedema;
  • Grade ≥ 2 ascites or pleural effusion;
  • Grade ≥ 2 or history of Grade ≥ 3 peripheral neuropathy;
  • Active uncontrolled bacterial or viral infection;
  • New York Heart Association Class ≥ III congestive heart failure;
  • Unstable angina pectoris or cardiac arrhythmia.
• Subjects must not have psychiatric illness/social situation that would limit compliance with the study.
• Subjects must not have a history of major immunologic reaction to any IgG containing agent.
• Subjects must not have any medical condition which in the opinion of the Investigator or Therapeutic Area Medical Director (TA MD) places the subject at an unacceptably high risk for toxicities.
• No known active severe acute respiratory syndrome conrona virus 2 (SARs-CoV2) infection. If a subject signs/symptoms suggestive of SARS-CoV2 infection, the subject must have a negative molecular (e.g., polymerase chain reaction {PRC} test result. in addition, if based on the answes to the SARS-CoV2 infection risk assissment tool the sire considers the subject currently at risk for developing SARCS-CoV2 infection, then the subject should wither be tested or advised to come back for the study screening after 14 days. 
  • At least 14 days have passed since first PRC test results have passed in asymptomatic patients or 14 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms (e.g., cough, shortness of breath);
    • Note: subjects who develop symptoms will follow guidance above for symptomatic subjects.
• Frequency or timing of COVID-19 testing and interval between testing for the above viral clearance criteria may be adjusted to account for epidemiological trends, updated information regarding infectivity and local institutional guidelines.
• For all females of child-bearing potential, a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.
• Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from Study Day 1 through at least 6 months after the last dose of study drug.
• Females who are not pregnant, breastfeeding, and are not considering becoming pregnant or donating eggs during the study or for approximately 6 months after the last dose of study drug.
• Males who are sexually active with female partner(s) of childbearing potential, must agree, from Study Day 1 through 6 months after the last dose of study drug, to practice the protocolspecified contraception.
• Males who are not considering fathering a child or donating sperm during the study or for approximately 6 months after the last dose of study drug.
• Subjects must not have received any live vaccine within 30 days of the first dose of investigational product.
• Treatment with any of the following therapies within the noted time intervals is excluded 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 thoracic cavity;
  • Within 4 weeks (28 days): 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.
• Treatment with any of the following therapies does not require a washout period:
  • Palliative radiation therapy for bone, skin, or subcutaneous metastases for 10 fractions or less; see above for CNS metastases;
  • Subjects currently treated with EGFR TKIs.
• Females, Non-Childbearing Potential Females do not need to use birth control during or following study drug treatment if considered of non-childbearing potential due to meeting any of the following criteria:
  • Postmenopausal, age > 55 years with no menses for 12 or more months without an alternative medical cause;
  • Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND a follicle-stimulating hormone (FSH) level > 30 IU/L;
  • Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy);
  • Females, of Childbearing Potential Females of childbearing potential must avoid pregnancy or breastfeeding while taking study drug(s) and for at least 6 months after the last dose of study drug. Females must commit to one of the following methods of birth control:  Combined (estrogen and progestogen containing) hormonal birth control (oral, intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at least 1 month prior to Study Day 1;
  • Progestogen-only hormonal birth control (oral, injectable, implantable) associated with inhibition of ovulation initiated at least 1 month prior to Study Day 1;
  • Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a hysterosalpingogram confirms success of the procedure);
  • Intrauterine device (IUD);
  • Intrauterine hormone-releasing system (IUS);
  • To have a vasectomized sexual partner(s) (the vasectomized partner[s] has received medical assessment of the surgical success and is the sole sexual partner of the trial subject);
  • To practice true abstinence, defined as: Refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, sympto-thermal, post-ovulation methods] and withdrawal are not acceptable). If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or sponge with spermicide should be used in addition to one of the birth control methods listed above (excluding true abstinence). Where confirmed as a local requirement, in addition to one form of highly effective contraception for women of childbearing potential, their male partner must agree to use condoms.
• Male subjects who are sexually active with a female partner of childbearing potential, must agree to use condoms, even if the male subject has undergone a successful vasectomy, and to not donate sperm from Study Day 1 through at least 6 months after the last dose of study drug.
• His female partner(s) must also use at least one of the following methods of birth control:
  • Combined (estrogen and progestogen containing) hormonal birth control (oral, intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at least 1 month prior to study Baseline Day 1;
  • Progestogen-only hormonal birth control (oral, injectable, implantable) associated with inhibition of ovulation initiated at least 1 month prior to study Day 1;
  • Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a hysterosalpingogram confirms success of the procedure);
  • IUD;
  • IUS.

Exclusion Criteria:

• Any negative response to above Inclusion Criteria.