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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Mar 2022 → ongoing

Decision date (initial)

2023-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-505749-14-00

EudraCT number

2021-001811-94

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy

The primary objective is to evaluate the efficacy of telisotuzumab vedotin compared with docetaxel on the basis of progression-free survival (PFS) and/or overall survival (OS) in the following nested populations:
- Subjects with c-Met high overexpressing, EGFR wildtype, nonsquamous NSCLC
and
- All subjects with c-Met overexpressing, EGFR wildtype, non-squamous NSCLC.

Secondary objectives 6

1. 1. Objective Response Rate (ORR) by BICR.
2. 2. Duration of Response (DoR) by BICR.
3. 3. Progression Free Survival per investigator assessment.
4. 4. Change from baseline to week 12 in physical functioning as measured by the physical functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQC30).
5. 5. Change from baseline to Week 12 in quality of life as measured by the global health status/quality of life domain of the EORTC QLQ-C30.
6. Safety and tolerability

Conditions and MedDRA coding

c-Met overexpressing EGFR wildtype non-squamous non-small cell lung cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subject must have c-Met overexpressing NSCLC as assessed by an AbbVie designated IHC laboratory using the VENTANA MET (SP44) RxDx assay
2. 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).
3. Subject must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.
4. Archival or fresh tumor material must be submitted for assessment of c-Met protein expression 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 (see Operations Manual Section 3.7). - If a subject 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
5. Subject has adequate bone marrow, renal, and hepatic function
6. Subject must have histologically or cytologically documented non-squamous cell NSCLC that is locally advanced or metastatic.
7. Subjects must have a known EGFR activating mutation status. - Subjects with EGFR activating mutations are not eligible.
8. Subjects with actionable alterations in genes other than EGFR are eligible.
9. Subject must have measurable disease per RECIST version 1.1.
10. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
11. 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.

Exclusion criteria 15

1. Subject has adenosquamous or neuroendocrine histology, or sarcomatoid features
2. 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.
3. Subject has received prior docetaxel therapy.
4. Subjects with metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery, radiotherapy or drug therapy) is provided and: - They are asymptomatic and off or on a stable or reducing dose of systemic steroids (on no more than 10 mg QD prednisone or equivalent) and/or anticonvulsants for at least 2 weeks prior to randomisation; - There is no evidence of new, untreated CNS metastases or progressing CNS metastases after treatment; - There is no evidence of leptomeningeal disease.
5. 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. Additionally, subjects must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without current evidence of disease.
6. 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.
7. History of prior radiation pneumonitis in the radiation field (fibrosis) is not permitted.
8. Subject with unresolved clinically significant AE ≥ Grade 2 from prior anticancer therapy, except for alopecia or anemia. Subjects with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
9. Subject has had major surgery within 21 days prior to randomisation.
10. 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.
11. 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) > 450 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.
12. Subject has a history of major immunologic reaction to any immunoglobulin G (IgG)-containing agent. Subject has hypersensitivity to docetaxel or polysorbate 80.
13. Subjects have received any live vaccine within 30 days of the first dose of study drug.
14. Treatment with any of the following therapies within the noted time intervals prior to randomisation: - Within 2 weeks (14 days): radiation therapy not involving the lungs. - Within 4 weeks (28 days) or 5 half-lives (whichever is shorter): systemic cytotoxic chemotherapy; small molecule targeted agents; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies.
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The co-primary endpoints are: Progression-Free Survival (PFS) per blinded independent central review (BICR); Overall Survival (OS)

Secondary endpoints 5

1. Objective Response Rate (ORR) by BICR
2. Duration of Response (DoR) by BICR
3. Change from baseline to Week 12 in physical functioning as measured by the physical functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30).
4. Change from baseline to Week 12 in quality of life as measured by the global health status/quality of life domain of the EORTC QLQ-C30.
5. PFS per investigator assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 14

Locations

16 EU/EEA countries · 99 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 130 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications