A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT04928846
• Recruitment Status: Recruiting
• First Posted: June 16, 2021
• Last Update Posted: May 14, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: June 14, 2021
• First Posted Date: June 16, 2021
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: March 25, 2022
• Estimated Primary Completion Date: June 7, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2021)

• Progression-Free Survival (PFS) per Independent Central Review (ICR) [ Time Frame: Up to approximately 39 months ]
  PFS is defined as the time from randomization to the first occurrence of radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) per ICR or death from any cause.
• Overall Survival (OS) [ Time Frame: Up to approximately 39 months ]
  OS is defined as the time from randomization to the event of death from any cause.

Original Primary Outcome Measures (submitted: June 14, 2021)

Progression-Free Survival (PFS) [ Time Frame: Up to approximately 39 months ]

PFS is defined as the time from randomization to the first occurrence of radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) per Independent Central Review (ICR) or death from any cause.

Current Secondary Outcome Measures (submitted: December 27, 2022)

• Objective Response Rate (ORR), per ICR. [ Time Frame: Up to approximately 58.25 months ]
  ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) based on RECIST v1.1
• Duration of Response (DoR), per ICR [ Time Frame: Up to approximately 58.25 months ]
  DoR is defined for responders as the time from response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause.
• PFS per Investigator Assessment [ Time Frame: Up to approximately 58.25 months ]
  PFS is defined as the time from randomization to the first occurrence of radiographic progression based on RECIST version 1.1 per investigator or death from any cause. Participants with no PFS event will be censored at the last evaluable radiographic assessment per investigator. Participants with no event and no evaluable post-baseline assessment will be censored at randomization.
• Time to Deterioration in Cough, Pain or Dyspnea as measured by the Cough, Pain and Dyspnea items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-LC13 is the lung cancer specific module of the core EORTC QLQ-C30. The QLQ-LC13 includes 13 questions that include both multi-item and single-item scales of lung cancer-associated symptoms (e.g., pain, coughing, hemoptysis, and dyspnea) and side-effects from chemo- and radiotherapy (e.g., hair loss, neuropathy, sore mouth and dysphagia). All scale and item scores are linearly transformed to a 0 to 100 scale, with higher scores representing increasing symptom levels or impacts.
• Time to Deterioration of Physical Functioning as measured by the Physical Functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30). [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden.
• Change from Baseline in Quality of Life as measured by the Global Health Status/Quality of Life Domain of the EORTC QLQ-C30. [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden.

Original Secondary Outcome Measures (submitted: June 14, 2021)

• Overall Survival (OS) [ Time Frame: Up to approximately 58.25 months ]
  OS is defined as the time from randomization to the event of death from any cause.
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 58.25 months ]
  ORR is defined as the percentage of subjects with a complete response (CR) or partial response (PR) based on RECIST v1.1, per ICR.
• Duration of Response (DoR) [ Time Frame: Up to approximately 58.25 months ]
  DoR is defined for responders as the time from response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause per ICR.
• Time to Deterioration in Cough, Pain or Dyspnea as measured by the Cough, Pain and Dyspnea items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-LC13 is the lung cancer specific module of the core EORTC QLQ-C30. The QLQ-LC13 includes 13 questions that include both multi-item and single-item scales of lung cancer-associated symptoms (e.g., pain, coughing, hemoptysis, and dyspnea) and side-effects from chemo- and radiotherapy (e.g., hair loss, neuropathy, sore mouth and dysphagia). All scale and item scores are linearly transformed to a 0 to 100 scale, with higher scores representing increasing symptom levels or impacts.
• Time to Deterioration of Physical Functioning as measured by the Physical Functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30). [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden.
• Change from Baseline in Quality of Life as measured by the Global Health Status/Quality of Life Domain of the EORTC QLQ-C30. [ Time Frame: Up to approximately 58.25 months ]
  The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
• Official Title: 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

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 determine if telisotuzumab vedotin works better than docetaxel and to assess how safe telisotuzumab vedotin is in adult participants with NSCLC who have previously been treated. 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 Teliso-V or Docetax at an 1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin or IV infusion of docetaxel. Approximately 698 adult participants with c-Met overexpressing NSCLC will be enrolled in the study in approximately 250 sites worldwide.

Participants will receive IV telisotuzumab vedotin every 2 weeks or docetaxel every 3 weeks until meeting study drug discontinuation criteria.

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Biological: Telisotuzumab Vedotin
  Intravenous (IV) Infusion
  Other Name: ABBV-399
• Drug: Docetaxel
  IV Infusion

Study Arms

• Experimental: Telisotuzumab Vedotin
  Participants will receive telisotuzumab vedotin every 2 weeks until meeting study drug discontinuation criteria.
  Intervention: Biological: Telisotuzumab Vedotin
• Active Comparator: Docetaxel
  Participants will receive docetaxel every 3 weeks until meeting study drug discontinuation criteria.
  Intervention: Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 14, 2021): 698
• Original Estimated Enrollment (submitted: June 14, 2021): 600
• Estimated Study Completion Date: March 21, 2028
• Estimated Primary Completion Date: June 7, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory using the VENTANA MET (SP44) RxDx assay.

• Archival or fresh tumor material must be submitted for assessment of c-Met levels during the Pre-Screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed.

  • 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).
• A histologically documented non-squamous cell NSCLC that is locally advanced or metastatic.
• A known epidermal growth factor receptor (EGFR) activating mutation status.
• Actionable alterations in genes other than EGFR .
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

• 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 will count as a prior line for eligibility purposes if progression occurred within 6 months of the end of therapy.

• Have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC:

  • Participants WITHOUT an actionable gene alteration: must have progressed on (or be considered ineligible for) platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).

  • Participants WITH an actionable gene alteration for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase [ALK] translocation): must have progressed on (or be considered ineligible for) anti-cancer therapy targeting driver gene alterations and platinum-based chemotherapy.

    • Participants 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).
• Must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.

• Participants 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.

Exclusion Criteria:

• Participants with adenosquamous histology.
• Actionable epidermal growth factor receptor (EGFR) activating mutations.
• Participants who have received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E..
• Participants who have received prior docetaxel therapy.

• 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.
• 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 computed tomography (CT) scan. A history of prior radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Unresolved adverse event (AE) >= Grade 2 from prior anticancer therapy, except for alopecia or anemia.
• Major surgery within 21 days prior to the first dose of telisotuzumab vedotin.
• Clinically significant condition(s) as listed in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Hungary, Russian Federation, Switzerland, Ukraine

Administrative Information

• NCT Number: NCT04928846
• Other Study ID Numbers: M18-868; 2021-001811-94 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: May 2024