ERIS: EGFR-Mutated Lung Cancer in Randomized Investigator-Initiated Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Jun 2022 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518172-31-01

EudraCT number

2021-003755-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the optimal sequence of EGFR-inhibitors.

Secondary objectives 1

1. To evaluate tumor response, adverse effects, and life quality of the study participants. To identify clinically relevant molecular profiles and biomarkers in blood and tumor for treatment decisions and management of resistance mechanisms.

Conditions and MedDRA coding

EGFR-mutated non-small cell lung cancer (NSCLC) not amenable for curative treatment intention and candidates for EGFR-inhibitor in first line.

Regulatory references

Plan to share IPD

Yes

IPD plan description

Deidentified participant data will be shared after finalisation of all planned publications and after the sponsors approval of the proposed use of the data.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written informed consent
2. Histological or cytological diagnosis of NSCLC.
3. Clinical stage III/IV disease or a recurrence not amenable for curative treatment intention.
4. Measurable disease according to RECIST 1.1 criteria or equivalent/modified criteria.
5. Any WHO PS.
6. Age 18 years or older.
7. EGFR-mutation in tumor (in cases where tumor tissue is not available for mutation analysis, circulating tumour-DNA (ctDNA) in plasma may serve as inclusion criteria).
8. Treatment-naive with regard to TKI’s.
9. For fertile participants, adequate contraception should be used; intrauterine device, bilateral tubal occlusion, vasectomy or abstinence (a reduced effect of hormonal contraception methods due to the drugs cannot be excluded). Pregnancy should be avoided during treatment and the first 4 months following treatment discontinuation.
10. Negative pregnancy test (blood or urine test)

Exclusion criteria 14

1. Condition incompatible with the study or with the planned treatment.
2. Severe hepatic impairment/renal function incompatible with study drug according to investigator.
3. Hereditary conditions with galactose intolerance, total lactase deficiency or glucose -galactose malabsorption.
4. Congenital long QT syndrome.
5. Judgment by the investigator that the subject should not participate in the study, e.g., if the subject is unlikely to comply with study procedures, restrictions and requirements.
6. Present second primary malignancy with metastatic potential.
7. Intake of hypericum perforatum (intake must be interrupted before start of study treatment).
8. All subjects should avoid concomitant use of medications with known interaction with planned treatment, whenever feasible. If the administration of a medication interacts with any of the three investigational treatments and cannot be exchanged or managed in order to avoid interactions the patient is excluded from the trial.
9. Any evidence of severe or uncontrolled systemic diseases which in the investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardise compliance with the protocol. Screening for chronic conditions is not required.
10. Gastrointestinal conditions incompatible with swallowing or precluding absorption of the study drug.
11. Pregnancy or refusal to use contraceptives.
12. Abnormal findings of blood chemistry not compatible with the study drug according to investigator.
13. History of hypersensitivity to the study drug (or drugs with a similar chemical structure or class) or any excipients.
14. Co-enrolment in other interventional trial if incompatible with ERIS according to investigator (e.g. due to potential drug interactions).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 12

1. Time to treatment failure (TTF) of EGFR-inhibitor sequence (total time on TKI)
2. Overall survival (OS)
3. Objective response rate (ORR) in first line and the entire sequence of treatment with EGFR-inhibitors
4. Disease control rate in (DCR) first line and the entire sequence of treatment with EGFR-inhibitors
5. Adverse events (AE)
6. Quality of life (QoL) as assessed through Lung Cancer Symptom Scale (LCSS)
7. Tumor-derived cell-free DNA, i.e. ctDNA, will be analyzed in plasma (and in some cases other fluids, e.g. pleural effusion) to search for potential resistance mechanisms to EGFR-TKIs, to identify early progression and to monitor treatment response. The sensitizing EGFR-mutation, EGFR T790M that confer EGFR-TKI resistance and possibly other tumor mutations, or genetic alterations will be analyzed, either alterations detected in pre-treatment tumor tissue or alterations being screened for in liqui
8. Proximity Extension Analysis (PEA) protein profiling and RNA expression analysis will be performed on tumor tissue. Obtained markers will subsequently be analyzed with exploratory bioinformatics to set up signaling networks possible to follow longitudinally during the disease course. Furthermore, biomarker candidates may be validated as potential drug candidates.
9. Bypass signaling is one reason of TKI-resistance. On tumor biopsies prior treatment, bypass signaling mechanisms with focus on Eph signaling components will be analyzed in situ. Upon relapse, the same reactions will be carried out on re-biopsies and differences will be evaluated in the context of response to EGFR-TKI.
10. Exosomes isolated from plasma and other body fluids will be profiled for mRNA, miRNA and proteins that could be potential key players in resistance mechanisms.
11. Copy number alterations analysis performed on tumor specimen prior treatment and when possible, on tumor re-biopsies at time of progression.
12. Tumor mutational burden (TMB, defined as mutations/megabase) on tumor tissue and potentially on longitudinally assembled blood will be evaluated as a potential marker of resistance and treatment response.

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Maria Planck

Public contact point

Organisation

Region Skane

Contact name

Maria Planck

Locations

1 EU/EEA country · 10 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 7 files

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

Application history

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