A trial to learn how effective and safe datopotamab deruxtecan (Dato-DXd) is compared to docetaxel and how well Dato-DXd works in adults with advanced or metastatic TROP2-positive, non-squamous non-small cell lung cancer (NS-NSCLC).

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

1 Apr 2026 → ongoing

Decision date (initial)

2026-03-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Safety

To assess the superiority of Dato-DXd relative to docetaxel by assessment of progression-free survival (PFS) by Blinded Independent Central Review (BICR) and overall survival (OS).

Secondary objectives 6

1. To assess the superiority of Dato-DXd relative to docetaxel by assessment of objective response rate (ORR), duration of response (DoR), and time to second progression or death (PFS2).
2. To evaluate exposure response relationship for efficacy and safety endpoints.
3. To investigate the immunogenicity of Dato-DXd.
4. To assess participant-reported lung cancer symptoms of NSCLC, physical functioning, and global health status (GHS)/quality of life (QoL) in participants treated with Dato-DXd relative to docetaxel.
5. To assess TROP2 diagnostic test performance and relationship with other tumour-derived biomarkers or diagnostics tests, and support diagnostic test development.
6. To assess the safety and tolerability of Dato-DXd relative to docetaxel.

Conditions and MedDRA coding

TROP2 NMR-positive advanced or metastatic non-squamous non-small cell lung cancer without actionable genomic alterations.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002976-PIP01-21, EMEA-002125-PIP01-17

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. Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous NSCLC without AGA at the time of randomisation and meets the criteria for NSCLC: * Participants must have documented negative test results for EGFR, ALK, and ROS1 genomic alterations. * Has no known tumour genomic alterations in NTRK, BRAF, RET, MET exon 14 skipping, KRAS G12C, HER2 or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies. * Prospectively assessed TROP2 QCS-NMR positive based on results from an appropriately validated investigational TROP2 RxDx device.
2. Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
3. Participants must have received platinum-based chemotherapy (PBC) in combination with anti-PD-1/anti-PD-L1 mAb as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
4. Provision of acceptable FFPE tumour sample for assessment of TROP2.
5. 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 ≥ 15mm) with CT or MRI and is suitable for accurate repeated measurements.
6. ECOG PS of 0 or 1.
7. Adequate bone marrow reserve and organ function within 7 days before randomisation.

Exclusion criteria 10

1. Squamous, mixed NSCLC, or SCLC histology.
2. NSCLC disease that is eligible for definitive local therapy alone.
3. History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence.
4. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation.
5. Clinically significant corneal disease.
6. Has active or uncontrolled hepatitis B or C virus infection.
7. Known HIV infection that is not well controlled.
8. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
9. History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
10. Has severe pulmonary function compromise per Investigator discretion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To assess the superiority of Dato-DXd vs docetaxel by assessment of PFS by BICR according to RECIST v1.1 in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA.
2. To assess the superiority of Dato-DXd vs docetaxel by assessment of OS in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA.

Secondary endpoints 8

1. Objective response rate (ORR)
2. Duration of response (DoR)
3. Time to second progression or death (PFS2)
4. Characterise population PK and its relationship with efficacy and safety endpoints, and evaluate the effects of covariates on PK, efficacy, and safety
5. Presence of antidrug antibody (ADAs) for Dato-DXd
6. Time to deterioration (TTD) in pulmonary symptoms, physical functioning, and in GHS/QoL
7. To assess TROP2 diagnostic test performance and relationship with other tumour-derived biomarkers or diagnostics tests, and support test development
8. To assess the safety and tolerability of Dato-DXd vs docetaxel in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA

Investigational products

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

Test 1

Comparator 1

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 Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Locations

8 EU/EEA countries · 56 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 83 files

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

Application history

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