A trial to learn how safe Dato-DXd is when given with osimertinib, and how well it works compared to osimertinib alone in people who have advanced or metastatic non-small cell lung cancer (NSCLC) with a mutation in the EGFR gene

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

9 Jan 2025 → ongoing

Decision date (initial)

2025-03-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-509883-89-00

ClinicalTrials.gov

NCT06350097

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To demonstrate the superiority of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of PFS by BICR in all randomised participants.

Secondary objectives 7

1. 1. To demonstrate the superiority of osimertinib+Dato-DXd vs osimertinib by OS assessment in all randomised participants.
2. 2. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib by PFS assessment on CNS metastases in participants with CNS metastases at baseline.
3. 3. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib by PFS assessment by investigator in all randomised participants.
4. 4. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib by ORR assessment in all randomised participants with measurable disease at baseline.
5. 5. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib by DoR assessment in all randomised participants with measurable disease at baseline.
6. 6. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib on the prevention of CNS metastases.
7. 7. To demonstrate the effectiveness of osimertinib+Dato-DXd vs osimertinib by PFS2 assessment.

Conditions and MedDRA coding

Epidermal growth factor receptor (EGFR) mutation-positive, locally advanced or metastatic non squamous non-small cell lung cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Participant must be ≥ 18 years
2. 2. Histologically or cytologically documented nonsquamous NSCLC.NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
3. 3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
4. 4. Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
5. 5. The tumour harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
6. 6. For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
7. 8. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.

Exclusion criteria 11

1. 2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
2. 4. Spinal cord compression and unstable brain metastases, as defined by Protocol.
3. 5. Clinically significant corneal disease.
4. 6. Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
5. 7. Known HIV infection that is not well controlled, as defined by Protocol.
6. 8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
7. 9. Resting ECG with clinically abnormal findings, as defined by Protocol.
8. 10. Uncontrolled or significant cardiac disease, as defined by Protocol.
9. 11. Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
10. 12. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.
11. 13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).

Secondary endpoints 7

1. 1. OS defined as the time from randomisation until the date of death due to any cause.
2. 2. Central nervous system progression-free survival (CNS PFS) is defined as the time from randomisation until the date of objective CNS progression assessed by CNS BICR or death (by any cause in absence of CNS progression).
3. 3. PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression).
4. 4. ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by BICR (and investigator) per RECIST 1.1.
5. 5. DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR (and investigator) assessment or death due to any cause. The measure of interest is the median of DoR.
6. 6. Neuro-radiologist assessments according to CNS RECIST 1.1 to determine the presence/absence of CNS lesions at progression in participants without CNS metastases at baseline.
7. 7. PFS2 will be defined as the time from randomisation to the earliest of the progression event (following the initial progression) subsequent to first subsequent anti-cancer therapy, or death.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

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

Locations

5 EU/EEA countries · 29 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 41 files

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

Application history

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