Phase 2, Open-Label Safety and Efficacy Study of Telisotuzumab Vedotin (ABBV-399) in Subjects with Previously Treated c-Met+ Non-Small Cell Lung Cancer

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

26 Mar 2019 → ongoing

Decision date (initial)

2023-12-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-507902-15-00

EudraCT number

2018-001772-38

ClinicalTrials.gov

NCT03539536

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Pharmacogenomic, Therapy, Safety

For Stage 1 and Stage 2:
The primary objective is to determine the overall response rate (ORR) of telisotuzumab vedotin in subjects with c-Met+ NSCLC.
For the Monotherapy Cohort 1.6 mg/kg Q2W:
Primary objective is to evaluate the safety and tolerability of telisotuzumab vedotin monotherapy dosed at 1.6 mg/kg Q2W.

Secondary objectives 2

1. For Stage 1 and Stage 2: The secondary objectives are to determine Duration of response (DoR), Disease control rate (DCR), Progression Free Survival (PFS), Overall Survival (OS), Safety and Tolerability.
2. For the Monotherapy Cohort 1.6 mg/kg Q2W: Secondary objective is to evaluate the preliminary efficacy of telisotuzumab vedotin monotherapy dosed at 1.6 mg/kg Q2W.

Conditions and MedDRA coding

Non-Small Cell Lung Cancer

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 10

1. Histologically confirmed non-small cell lung cancer (NSCLC) with known non squamous epidermal growth factor receptor (EGFR) status (wild type; with site documented status). Subjects in Monotherapy Cohort 1.6 mg/kg Q2W must have non-squamous EGFR wild type NSCLC.
2. Has locally advanced or metastatic NSCLC.
3. Has c-Met+ NSCLC as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory. Subject must submit archival or fresh tumor material for assessment of c-Met levels during the pre­screening 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. "
4. If a subject meets eligibility criteria for c-Met protein expression level based on archival tumor material, fresh tumor material for assessment of c-Met expression levels should be submitted prior to dosing of telisotuzumab vedotin. If it is determined that a pre-dose fresh biopsy is not appropriate for a given subject, the subject may still be enrolled at the investigator's discretion. AbbVie must be informed of this decision before dosing. "
5. Subjects who 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).
6. Subject must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of prior systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.
7. Subjects should not have received prior cMET-targeted antibody therapies.
8. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
9. 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 result or 2 negative antigen test results at least 24 hours apart. "
10. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria: - At least 10 days since first positive test result has passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms. "

Exclusion criteria 14

1. Has adenosquamous histology.
2. 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. "
3. Has a clinically significant condition(s) described in the protocol.
4. Has unresolved clinically significant adverse events >= grade 2 from prior anticancer therapy, except for alopecia or anemia. "
5. Had major surgery within 21 days prior to the first dose of telisotuzumab vedotin. "
6. Subject must not have a history of interstitial lung disease or pneumonitis that required treatment with systemic steroids. "
7. 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. For imaging findings deemed clinically insignificant by the treating physician, subject may be eligible after discussion with and approval from the AbbVie medical monitor. "
8. For Sites in Ireland Only: Subjects must not have any evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or ILD. For imaging findings deemed clinically insignificant by the treating physician, subject may be eligible after discussion with and approval from the AbbVie medical monitor. "
9. Subjects must not have received radiation therapy to the lung <6 months prior to the first dose of telisotuzumab vedotin. "
10. Subjects must not have received any live vaccine within 30 days of the first dose of investigational product.
11. For Sites in France and Czech Republic Only: Subjects must not have 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."
12. For Sites in France and Czech Republic Only: Subjects must not have Active hepatitis B virus (HBV) infection, defined by hepatitis B surface antigen (HBsAg) positivity or 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.
13. For Sites in France and Czech Republic Only: Subjects must not have 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. "
14. For Sites in France and Czech Republic Only: Subjects must not have Uncontrolled autoimmune disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Response Rate (ORR)

Secondary endpoints 4

1. Duration of Response (DoR)
2. Disease Control Rate (DCR)
3. Progression-Free Survival (PFS)
4. Overall Survival (OS)

Investigational products

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

Test 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 5

Sponsor responsibilities

Article 77 implementation

AbbVie Deutschland GmbH & Co. KG

Locations

8 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 61 files

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

Application history

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