A trial to learn if Dato-DXd with rilvegostomig, or rilvegostomig alone, is safe and works compared with pembrolizumab in people who have advanced non-squamous non-small cell lung cancer (NSCLC) with high levels of the PD-L1 protein

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

28 Jan 2025 → ongoing

Decision date (initial)

2024-06-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ASTRAZENECA AB

External identifiers

EU CT number

2023-505077-32-00

ClinicalTrials.gov

NCT06357533

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Pharmacokinetic, Safety, Efficacy, Pharmacoeconomic

1. To demonstrate the superiority of the Dato-DXd in combination with rilvegostomig relative to pembrolizumab by assessment of PFS by BICR in TROP2 biomarker positive participants.
2. To demonstrate the superiority of Dato-DXd in combination with rilvegostomig relative to pembrolizumab by assessment of OS in TROP2 biomarker positive participants.

Secondary objectives 2

1. To demonstrate the superiority of Dato-DXd in combination with rilvegostomig relative to pembrolizumab by assessment of PFS by BICR in the FAS population.
2. To demonstrate the superiority of Dato-DXd in combination with rilvegostomig relative to pembrolizumab by assessment of OS in the FAS population.

Conditions and MedDRA coding

Locally-advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Study design 3 periods

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 9

1. Histologically or cytologically documented non-squamous NSCLC.
2. Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation.
3. Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and abscence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies.
4. Must provide an available FFPE tumour sample collected ≤ 3 months prior to the start of screening. If such a sample is not available, then a FFPE tumour sample will be collected at biomarker screening (if applicable) or main screening.
5. Known tumour PD-L1 expression status defined as TC ≥ 50%, determined prospectively using an FFPE tumour sample collected using the VENTANA PD-L1 (SP263) Assay).
6. At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline.
7. ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior randomisation.
8. Adequate bone marrow reserve and organ function as defined in inclusion criteria 13.
9. Prior to the availability of the VENTANA TROP2 device, retrospective tumour material confirms eligibility. Once the VENTANA TROP2 device is available, prospective testing is implemented.

Exclusion criteria 13

1. Prior systemic therapy for advanced/metastatic NSCLC.
2. Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
3. History of another primary malignancy within 3 years.
4. Active or prior documented autoimmune or inflammatory disorders (with exceptions).
5. Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, serious chronic gastrointestinal conditions, cardiac disease.
6. Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
7. History of any ILD/pneumonitis, including radiation pneumonitis, or drug- induced ILD/pneumonitis, has current or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
8. Has significant pulmonary function compromise, as determined by the investigator
9. Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
10. History of leptomeningeal carcinomatosis
11. Known clinically significant corneal disease
12. Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
13. History of active primary immunodeficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Assessment of PFS by BICR in TROP2 biomarker positive participants.
2. Assessment of OS in TROP2 biomarker positive participants.

Secondary endpoints 8

1. Assessment of PFS by BICR in the FAS population.
2. Assessment of OS in the FAS population.
3. Objective Response Rate (ORR), Duration of Response (DoR)
4. Participant-reported lung cancer symptoms of NSCLC and participant-reported GHS/QOL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab
5. Pharmacokinetics (PK)
6. Immunogenicity
7. Second Progression-Free Survival (PFS2)
8. Safety and tolerabillity evaluated in terms of AEs

Investigational products

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

Test 2

Comparator 1

Auxiliary 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

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

7 EU/EEA countries · 63 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 84 files

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

Application history

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