An open-label, single-arm, Phase II, multinational, multicentre study to assess the efficacy and safety of 5 years of osimertinib in participants with epidermal growth factor receptor mutation-positive Stage II-IIIB non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy (TARGET)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Feb 2023 → ongoing

Decision date (initial)

2024-03-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astrazeneca AB

External identifiers

EU CT number

2023-508740-21-00

EudraCT number

2021-003024-33

ClinicalTrials.gov

NCT05526755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacogenomic, Safety, Pharmacodynamic, Efficacy

To estimate the efficacy of adjuvant osimertinib measured by DFS at 5years, in the FAS. (Common EGFRm Cohort)

Secondary objectives 4

1. To estimate the efficacy of adjuvant osimertinib measured by DFS at 3, 4, and 5 years (Uncommon EGFRm Cohort)
2. To further assess other parameters of efficacy of 3, 4, and 5 years of adjuvant osimertinib (Common EGFRm Cohort)
3. To assess the safety and tolerability of 5 years of adjuvant osimertinib (both cohorts)
4. To assess recurrence events (both cohorts)

Conditions and MedDRA coding

Non-Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provision of informed consent prior to any study specific procedures.
2. Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICFs and in this protocol
3. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative
4. Male or female, aged at least 18 years.
5. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
6. MRI or contrast CT scan of the brain must be done prior to surgery as it is considered standard of care. Participants in whom this was not done within 42 days (6 weeks) prior to surgery may still be enrolled if appropriate imaging is performed prior to enrolment, ie, MRI or CT of the brain.
7. Participants must be classified post-operatively as Stage II, IIIA, or IIIB on the basis of surgical pathologic criteria. Staging will be according to the pTNM (pathologic tumour, node, metastasis) staging system for lung cancer (AJCC 8th Edition Staging Manual
8. Confirmation by the local laboratory that the tumour harbours one of the following EGFR mutations: -1 of the 2 common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo T790M and excluding all exon 20 insertions (Common EGFRm Cohort); or - Uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort)
9. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. Resection may be accomplished by open or Video Associated Thoracic Surgery techniques

Exclusion criteria 9

1. Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study drug
2. Participants currently receiving (or unable to stop use prior to receiving the first dose of study intervention) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to first dose) (Appendix G). All participants must try to avoid concomitant use of any medications, herbal supplements, and/or ingestion of food with known inducer effects on CYP3A4. Participants with any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy will not be eligible.
3. Participants who have had only segmentectomies or wedge resections
4. History of other malignancies, except: adequately treated non- melanoma skin cancer, curatively treated in situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years before the start of study intervention and that, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy
5. 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 participant to participate in the study or that would jeopardise compliance with the protocol; or active infection (eg, participants receiving treatment for infection including, hepatitis C and human immunodeficiency virus, or active, uncontrolled HBV infection). - Screening for chronic conditions is not required. - Active infection will include any participants receiving treatment for infection. Should participants with HBV infection be included, they are only eligible if they meet all the following criteria: -Demonstrated absence of HCV co-infection or history of HCV co-infection -Demonstrated absence of HIV infection -Participants with active HBV infection are eligible if they are: Receiving anti-viral treatment for at least 6 weeks prior to study intervention, HBV DNA is suppressed to < 100 IU/mL and transaminase levels are below ULN. - Participants with a resolved or chronic HBV infection are eligible if they are: Negative for HBsAg and positive for hepatitis B core antibody (anti-HBc IgG or total anti-HBc Ab). In addition, participants must be receiving anti-viral prophylaxis for 2 to 4 weeks prior to study intervention. Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below < 100 IU/mL (ie, are in an inactive carrier state). In addition, participants must be receiving anti-viral prophylaxis for 2 to 4 weeks prior to study intervention. Refer to Section 5.3. Should participants with HIV infection be included, they are only eligible if they meet all the following criteria: − Demonstrated absence of HBV/HCV co-infection − Undetectable viral RNA load for 6 months − CD4+ count of > 350 cells/μL − No history of acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months − Stable for at least 4 weeks on the same anti-HIV medications
6. 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
7. Any of the following cardiac criteria: - Mean resting QTc interval > 470 msec, obtained from 3 ECGs. - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block. - Participant with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including: o Serum/plasma potassium < LLN o Serum/plasma magnesium < LLN o Serum/plasma calcium < LLN - Heart failure, congenital long QT interval (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 TdP.
8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
9. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: - Absolute neutrophil count < 1.5 × 109 /L. - Platelet count < 100 × 109 /L. - Haemoglobin < 90 g/L. - ALT > 2.5 × the ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. - AST > 2.5 × ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. - Total bilirubin > 1.5 × ULN if no liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases. - Creatinine > 1.5 × ULN concurrent with CrCl < 50 mL/min (measured or calculated by Cockcroft and Gault equation, Appendix K); confirmation of CrCl is only required when creatinine is > 1.5 × ULN

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. DFS at 5 years per the investigator's assessment in the Common EGFRm Cohort

Secondary endpoints 3

1. The measure of interest is the proportion of participants alive and disease-free at 3, 4, and 5 years
2. The measure of interest is the proportion of participants alive and disease-free at 3 and 4 years
3. The measure of interest is the proportion of participants alive at 3, 4, and 5 years

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical study Information Centre

Third parties 1

Locations

2 EU/EEA countries · 21 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 28 files

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

Application history

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