Utility of analysis in blood of the evolution of the drug brigatinib for patients with lung cancer with ALK mutations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion GECP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 May 2020 → ongoing

Decision date (initial)

2024-03-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

External identifiers

EU CT number

2024-511317-38-00

EudraCT number

2019-002369-36

ClinicalTrials.gov

NCT04223596

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the Overall response rate (ORR) of brigatinib as measured by investigator. Overall response will be assessed per RECIST V1.1 criteria

Secondary objectives 6

1. To evaluate the efficacy of brigatinib as measured by investigator. Assessed as duration of response (DOR) according to RECIST v1.1.
2. To evaluate the efficacy of brigatinib as measured by investigator. Assessed as time on treatment according to RECIST v1.1.
3. To evaluate the intracranial overall response rate (ORR) and the intracranial time to progression
4. To evaluate the PFS rate at 1 year and 2 years of treatment with brigatinib by RECIST v1.1
5. To evaluate the Overall Survival (OS) rate at 1 year and 2 years of treatment with brigatinib
6. To evaluate the safety and tolerability of brigatinib.

Conditions and MedDRA coding

ALK+ non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Male or female, aged equal or greater ≥18 years old
2. ECOG performance status of 0-2
3. Histologically or cytologically confirmed, Stage IIIB or IV NSCLC
4. Patients who have documented locally ALK rearrangement
5. No prior treatment for Stage IIIB or IV non-squamous NSCLC.
6. Having a life expectancy ≥ 3 months
7. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy.
8. Untreated or treated CNS metastases allowed, as long as asymptomatic and neurologically stable
9. Patients with at least 1 measurable lesion, as defined by RECIST v1.1
10. Normal QT interval (QT) on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤ 450 milliseconds (msec) in males of ≤ 470 msec in females
11. Adequate hematologic and organ function
12. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
13. Willingness and ability to comply with scheduled visits and study procedures
14. For female patients of childbearing potential, a negative pregnancy test must have been documented prior to enrollment (within 14 days prior to enrollment)

Exclusion criteria 14

1. Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, STK-1 Ligand alteration, MDM2 amplification or ROS1 translocations.
2. Patients that received any prior TKI, including ALK-targeted TKIs or any systemic anticancer therapy for locally advanced or metastasic disease
3. Patients that have received chemotherapy or radiation within 14 days of first dose of study drug.
4. Symptomatic CNS metastases (parenchymal or leptomeningeal) that are neurologically unstable or required an increasing dose of corticosteroids within 7 days prior to first dose of study drug
5. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression is allowed.
6. Malignancies other than NSCLC within 3 years prior to enrollment
7. Women who are pregnant, lactating, or intending to become pregnant during the study
8. Patients that received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib
9. History of idiopathic pulmonary fibrosis, pulmonary interstitial disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
10. Have uncontrolled hypertension
11. Positive test for HIV. A and patients with active hepatitis B or active tuberculosis
12. Severe infections within 2 weeks prior to be included in the study
13. Have significant, uncontrolled or active cardiovascular disease
14. Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate

Secondary endpoints 5

1. Duration of response (DOR)
2. Intracranial overall response rate
3. PFS rate at 1 year and 2 years
4. Overall Survival (OS) rate at 1 year and 2 years
5. Safety and tolerability of brigatinib

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Scientific contact point

Organisation

Fundacion GECP

Contact name

Mariano Provencio

Public contact point

Organisation

Fundacion GECP

Contact name

Maria Fernández

Locations

1 EU/EEA country · 15 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 9 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