First line treatment with osimertinib in non-small cell lung cancer, coupled with studies on biological samples.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vestre Viken HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Nov 2018 → 31 Oct 2025

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513881-20-00

EudraCT number

2018-001863-21

ClinicalTrials.gov

NCT03804580

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

To assess the efficacy of osimertinib by assessment of objective response rate (ORR)

Secondary objectives 15

1. Assess efficacy of osimertinib by assessment in terms of progression free survival (PFS)
2. Assess efficacy of osimertinib by assessment in terms of duration of response (DoR)
3. Assess efficacy of osimertinib by assessment in terms of disease control rate (DCR)
4. Assess efficacy of osimertinib by assessment in terms of intracranial ORR
5. Assess efficacy of osimertinib by assessment in terms of Intracranial DoR
6. Assess efficacy of osimertinib by assessment in terms of intracranial progression free survival (iPFS)
7. Assess efficacy of osimertinib by assessment in terms of tumour shrinkage
8. Assess efficacy of osimertinib by assessment in terms of overall survival (OS)
9. To confirm the safety profile of osimertinib
10. Exploratory objectives like Molecular characterization of blood and tissue before commencement on osimertinib, and at progression on osimertinib
11. Exploratory objectives like NGS (deep sequencing) of tumour tissue
12. Exploratory objectives like array-based microRNA, methylation, mRNA expression
13. Exploratory objectives like immunohistochemistry (IHC) on AXL, cMET, CD73 etc
14. Exploratory objectives like exploratory analyses to be determined
15. Mutational analyses (ctDNA) and conventional tumour markers during therapy

Conditions and MedDRA coding

EGFR-mutated non-small cell lung cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provision of signed and dated, written informed consent.
2. Age > 18 years.
3. Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy. Patients that have received systemic adjuvant therapy for non-metastatic disease in the past will need a new biopsy before inclusion.
4. Documented EGFR mutation in exon 18-21, except insertions in exon 20, based on tissue analysis
5. ECOG status 0-2 and a minimum life expectancy of 12 weeks.
6. Patients with untreated, mild or moderately symptomatic and measurable brain metastases are eligible, but will be allocated to cohort A (see excl. point 6). Patients with pre-treated, stable and asymptomatic brain metastases will be allocated to cohort B.
7. At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1.
8. Females should be using adequate contraceptive measures (see appendix E), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:  Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments  Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution  Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
9. Male subjects must be willing to use barrier contraception

Exclusion criteria 18

1. Previous systemic treatment against metastatic NSCLC.
2. Major surgery within 4 weeks of inclusion
3. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of inclusion
4. Subjects currently receiving (or unable to stop using) potent inducers of CYP3A4. Patients must stop using CYP3A4 inducers at least 3 weeks prior to treatment with osimertinib
5. Subjects with spinal cord compression unless they have completed definitive therapy, are not on steroids and have had a stable neurological status for at least 2 weeks after completion of definitive therapy and steroids.
6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
7. Previous malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry.
8. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
9. Exclude based on any of the following cardiac criteria:  Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value  Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block  Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: serum/plasma potassium < LLN; serum/plasma magnesium < LLN; serum/plasma calcium < LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
11. Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:  Absolute neutrophil count < 1.5 x 109/L  Platelet count < 100 x 109/L  Haemoglobin < 90 g/L  Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases  Aspartate aminotransferase (AST) > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases  Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or liver metastases  Serum creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min [measured or calculated by Cockcroft and Gault equation]—confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
12. History of hypersensitivity of active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
13. Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
14. Previous enrolment in the present study or previous treatment with osimertinib.
15. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy-related neuropathy.
16. Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry
17. Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site).
18. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the efficacy of osimertinib by assessment of objective response rate (ORR).

Secondary endpoints 15

1. To further assess the efficacy of osimertinib in terms of Progression free survival (PFS)
2. To further assess the efficacy of osimertinib in terms of Duration of Response (DoR)
3. To further assess the efficacy of osimertinib in terms of Disease Control Rate (DCR)
4. To further assess the efficacy of osimertinib in terms of Intracranial ORR
5. To further assess the efficacy of osimertinib in terms of intracranial DoR
6. To further assess the efficacy of osimertinib in terms of intracranial progression free survival (iPFS)
7. To further assess the efficacy of osimertinib in terms of tumour shrinkage
8. To further assess the efficacy of osimertinib in terms of overall survival (OS)
9. To confirm the safety profile of osimertinib
10. Exploratory objectives Molecular characterization of blood and tissue before commencement on osimertinib, and at progression on osimertinib
11. Exploratory objectives: NGS (deep sequencing) of tumour tissue
12. Exploratory objectives: Array-based microRNA, methylation, mRNA expression
13. Exploratory objectives : Immunohistochemistry (IHC) on AXL, cMET, CD73 etc
14. Exploratory objectives: Exploratory analyses to be determined
15. Mutational analyses (ctDNA) and conventional tumour markers during therapy

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vestre Viken HF

Sponsor organisation

Vestre Viken HF

Address

Groenland 32

City

Drammen

Postcode

3045

Country

Norway

Scientific contact point

Organisation

Vestre Viken HF

Contact name

Siri Bråthen

Public contact point

Organisation

Vestre Viken HF

Contact name

Siri Bråthen

Locations

3 EU/EEA countries · 5 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 11 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