A trial to learn how safe Dato-DXd is and how well it works in people with NSCLC that has advanced after receiving osimertinib

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

18 Feb 2026 → ongoing

Decision date (initial)

2024-11-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511362-37-00

ClinicalTrials.gov

NCT06417814

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the superiority of Dato-DXd monotherapy compared to chemotherapy in terms of PFS.
To demonstrate the superiority of Dato DXd combined with osimertinib compared to chemotherapy in terms of PFS.

Secondary objectives 2

1. To assess the superiority of Dato-DXd with or without osimertinib compared to chemotherapy in terms of OS.
2. To assess the superiority of Dato-DXd with or without osimertinib compared to chemotherapy in terms of BICR-assessed CNS PFS.

Conditions and MedDRA coding

Non squamous non-small cell lung cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

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. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically or cytologically confirmed non-squamous NSCLC.
2. Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKis] sensitivity [Ex19del, L858R, G719X, S768I, or L861Q], either alone or in combination with other EGFR mutations, which may include T790M).
3. Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
4. Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
5. At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Adequate bone marrow reserve and organ function within 7 days before randomization.

Exclusion criteria 11

1. Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the palliative setting. Platinum-based chemotherapy in curative setting within 12 months prior to randomization.
2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
3. Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
4. Has significant third-space fluid retention (example [eg.], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
5. History of ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
6. Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
7. Unstable spinal cord compression and/or unstable brain metastases.
8. Participants with symptomatic brain metastases (including leptomeningeal involvement).
9. Clinically significant corneal disease.
10. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
11. Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as the time from randomization to BICR assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti cancer therapy, or clinical progression.

Secondary endpoints 12

1. Overall Survival (OS) is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants, as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy.
2. Central Nervous System Progression-free Survival (CNS PFS) is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR-confirmed CNS modified RECIST v1.1 progression.
3. Objective Response Rate (ORR) is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1.
4. Duration of Response (DoR) is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause.
5. Progression-free Survival-2 (PFS-2) is defined as the time from randomization to the earliest of the progression event (following the initial investigator assessed progression), after first subsequent therapy, or death.
6. ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, using CNS modified RECIST v1.1.
7. DoR is defined as the time from the date of first documented response until date of documented progression or death due to any cause using CNS modified RECIST v1.1.
8. Time to deterioration (in pulmonary symptoms [dyspnea, cough, and chest pain]) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
9. Time to deterioration in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form 8c will be evaluated. Time to deterioration (in physical functionating) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
10. Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172 will be reported. Time to deterioration (in GHS/QoL) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
11. Concentration of Dato-DXd, total anti-TROP2 antibody and DXd in plasma.
12. Presence of antidrug antibody (ADAs) for Dato-DXd (confirmatory results: positive or negative, titers).

Investigational products

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

Test 3

Comparator 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

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 2

Locations

7 EU/EEA countries · 78 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 7 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 124 files

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

Application history

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