A Study of Dato-DXd in Combination With Durvalumab and Carboplatin for First-line Treatment of Advanced NSCLC Without Actionable Genomic Alterations

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

5 Jan 2023 → ongoing

Decision date (initial)

2024-06-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505993-14-00

EudraCT number

2021-004606-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Therapy, Safety

To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:
1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

Secondary objectives 1

1. To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy in ITT, non-squamous and TROP2 biomarker-defined populations, by assessment of PFS by BICR, OS, ORR by BICR, DoR by BICR and investigator assessment, PFS by investigator assessment, and time to second progression or death, clinical outcomes assessments, pharmacokinetics, and immunogenicity.

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC)

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 6

1. Participants ≥ 18 years at screening
2. Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
3. Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations). Testing is not required for tumors with squamous histology, with exceptions.
4. ECOG PS of 0 or 1
5. Archival tumour tissue
6. Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion criteria 9

1. Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
2. History of another primary malignancy with exceptions
3. Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
4. Spinal cord compression or clinically or radiologically active brain metastases
5. History of leptomeningeal carcinomatosis.
6. Known active or uncontrolled hepatitis B or C virus infection.
7. Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
8. Clinically significant corneal disease
9. History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Progression-Free Survival as assessed by BICR in non-squamous TROP2 biomarker positive analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.
2. Overall Survival in non-squamous TROP2 biomarker positive analysis set, defined as the time from randomisation until the date of death due to any cause
3. Progression-Free Survival as assessed by BICR in non-squamous full analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.
4. Overall Survival in non-squamous full analysis set, defined as the time from randomisation until the date of death due to any cause

Secondary endpoints 4

1. Progression-Free Survival as assessed by BICR, Overall Survival, Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Time to second progression or death in ITT and TROP2 biomarker-defined populations
2. Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Progression-Free Survival 2 in the non-squamous population
3. Clinical Outcome Assessments as measured by the NSCLC-SAQ and PROMIS Physical Function short form 8c.
4. Pharmacokinetics and immunogenicity

Investigational products

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

Test 3

Comparator 4

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

Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Center

Locations

10 EU/EEA countries · 81 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 80 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