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)

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

Overview

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 80 to 90 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.

Interventions

• Drug Telisotuzumab Vedotin
  Intravenous (IV) Infusion

Primary outcome measures

• Percentage of Participants with Treatment-Emergent Adverse Events (AE)s (Any-grade and Grade >= 2) [Time frame: Up to Approximately 3 Years]
• Percentage of Participants with Treatment-Emergent Interstitial Lung Disease (ILD) [Time frame: Up to Approximately 3 Years]
• Percentage of Participants with Treatment-Emergent Peripheral Neuropathy [Time frame: Up to Approximately 3 Years]
• Percentage of Participants with Treatment-Emergent Ocular Surface Disorders [Time frame: Up to Approximately 3 Years]
• Percentage of Participants with Treatment-Emergent AEs Leading to Study Drug Discontinuation [Time frame: Up to Approximately 3 Years]
• Percentage of Participants with Grade 5 Treatment-Emergent AEs [Time frame: Up to Approximately 3 Years]
• Objective Response (OR) by Blinded Independent Central Review (BICR) [Time frame: Up to Approximately 3 Years]

Secondary outcome measures (9)

• Concentrations of Telisotuzumab Vedotin Conjugate in Serum [Time frame: Up to 26 Weeks]
• Concentrations of Monomethylauristatin E (MMAE) Payload in Plasma [Time frame: Up to 26 Weeks]
• Percentage of Participants with Antidrug Antibodies (ADAs) of Telisotuzumab Vedotin [Time frame: Up to 26 Weeks]
• Percentage of Participants with Neutralizing Antidrug Antibodies (nADAs) of Telisotuzumab Vedotin [Time frame: Up to 26 Weeks]
• Change in Selected items of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Time frame: Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years]
• Change in GP5 item of the Functional Assessment of Cancer Therapy-General (FACT-G) [Time frame: Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years]
• Duration of Response (DoR) by BICR [Time frame: Up to Approximately 3 Years]
• Progression-Free Survival (PFS) by BICR [Time frame: Up to Approximately 3 Years]
• Overall Survival (OS) [Time frame: Up to Approximately 3 Years]

Eligibility criteria

Inclusion criteria

• Projected life expectancy of at least 12 weeks.
• Must have c-Met overexpressing non-small cell lung cancer (NSCLC) (defined as >= 25% tumor cells with 3+ staining (high \[>= 50% 3+\]; intermediate \[>= 25% - < 50%\]) as assessed by a Sponsor 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.
• EGFR activating mutations (e.g., EGFR Exon 19 deletions, T790M, Exon 21 L858R, or Exon 20 insertion 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 39 centers

• Ironwood Cancer and Research Center /ID# 276370 — Chandler
• University of Arkansas for Medical Sciences /ID# 272923 — Little Rock
• Valkyrie Clinical Trials /ID# 271322 — Los Angeles
• Yale New Haven Hospital /ID# 271584 — New Haven
• Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 270899 — Jacksonville
• Ocala Oncology Center /ID# 273697 — Ocala
• Memorial Hospital West /ID# 270313 — Pembroke Pines
• Comprehensive Hematology Oncology /ID# 270422 — St. Petersburg
• … and 31 more centers

China · 10 centers

• Beijing Chest Tumor Hospital /ID# 271935 — Beijing
• Fujian Province Cancer Hospital /ID# 276178 — Fuzhou
• Affiliated Cancer Hospital of Guangxi Medical University /ID# 271931 — Nanning
• Harbin Medical University Cancer Hospital /ID# 271665 — Harbin
• Henan Cancer Hospital /ID# 271927 — Zhengzhou
• Union Hospital - Tongji Medical College /ID# 271668 — Wuhan
• The First Affiliated Hospital of Nanchang University /ID# 271666 — Nanchang
• The First Affiliated Hospital of Xi'an Jiaotong University /ID# 271928 — Xi'an
• … and 2 more centers

Japan · 10 centers

• Nagoya University Hospital /ID# 277010 — Nagoya
• National Cancer Center Hospital East /ID# 277056 — Kashiwa-shi
• Hokkaido University Hospital /ID# 277014 — Sapporo
• Kobe Minimally Invasive Cancer Center /ID# 277469 — Kobe
• Kitasato University Hospital /ID# 277012 — Sagamihara-shi
• Sendai Kousei Hospital /ID# 277023 — Sendai
• University of Miyazaki Hospital /ID# 277020 — Miyazaki
• Kurashiki Central Hospital /ID# 276995 — Kurashiki-shi
• … and 2 more centers

Brazil · 7 centers

• Suporte Nutricional e Quimioterapia LTDA - PRONUTRIR /ID# 273203 — Fortaleza
• Ictrials Pesquisa E Desenvolvimento /ID# 276681 — Curitiba
• Hospital De Câncer De Pernambuco /ID# 276104 — Recife
• Liga Norte Riograndense Contra O Cancer /ID# 273183 — Natal
• Oncosite - Centro de Pesquisa Clinica em Oncologia /ID# 272513 — Ijuí
• Cepen - Centro De Pesquisa E Ensino Em Oncologia De Santa Catarina /ID# 273204 — Florianópolis
• Hospital Alemao Oswaldo Cruz - Sao Paulo /ID# 272512 — São Paulo

Serbia · 7 centers

• Institute for Oncology and Radiology of Serbia /ID# 270561 — Belgrade
• Military Medical Academy /ID# 279873 — Belgrade
• University Clinical Center Serbia /ID# 270808 — Belgrade
• Clinical Hospital Center - Bezanijska Kosa /ID# 270558 — Belgrade
• University Clinical Center Nis /ID# 270557 — Niš
• Institute For Pulmonary Diseases Of Vojvodina /ID# 270559 — Kamenitz
• University Clinical Center Kragujevac /ID# 275773 — Kragujevac

Israel · 5 centers

• Meir Medical Center /ID# 270071 — Kefar Sava
• Rabin Medical Center. /ID# 270087 — Petah Tikva
• The Chaim Sheba Medical Center /ID# 270068 — Ramat Gan
• Rambam Health Care Campus- Haifa /ID# 270078 — Haifa
• Shaare Zedek Medical Center /ID# 270095 — Jerusalem

Singapore · 2 centers

• National Cancer Centre Singapore /ID# 271499 — Singapore
• National University Hospital /ID# 271700 — Singapore

Identifiers

NCT: NCT06568939 · M25-274

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗