Phase III, Open-label, Study of First-line Dato-DXd in Combination WithRilvegostomig for Advanced Non-squamous NSCLC With High PD-L1Expression (TC>=50%) and Without Actionable Genomic Alterations

JRCT ID: jRCT2031240095

Registered date:20/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-Small Cell Lung Cancer
• Date of first enrollment: 01/04/2024
• Target sample size: 67
• Countries of recruitment: Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Germany,Japan,Hungary,Japan,India,Japan,Italy,Japan,Poland,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States of America,Japan
• Study type: Interventional

Intervention(s)

Arm 1: Dato-DXd in Combination With Rilvegostomig
Participants in the Dato-DXd incombination with Rilvegostomig groupwill receive Dato-DXd plusrilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1of each 21-day cycle.

Arm 2: Rilvegostomig Monotherapy
Participants in the rilvegostomigmonotherapy group will receiverilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1of each 21-day cycle.

Arm 3: Pembrolizumab Monotherapy
Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3weeks (Q3W) on Day 1 of each 21-daycycle.

Outcome(s)

Primary Outcome

- Progression-Free Survival (PFS) inTROP2 biomarker positive participants. [Time Frame: Approximately 4 years]
PFS is defined as time fromrandomisation until progression perRECIST 1.1 as assessed by BICR, ordeath due to any cause. The analysis will include allrandomised participants, asrandomised, regardless of whether theparticipant withdraws fromrandomised therapy, receives anotheranti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the followingpopulation:

_TROP2 biomarker positive population
The B167is the HR of PFS.
PFS by investigator will be reported as a sensitivity analysis.

- Overall Survival (OS) in TROP2 biomarker positive participants. [Time Frame: Approximately 6 years]
OS is defined as the time fromrandomisation until the date of deathdue to any cause. The analysis will include allrandomised participants, asrandomised, regardless of whether theparticipant withdraws fromrandomised therapy or receivesanother anti-cancer therapy, in thefollowing population:

_TROP2 biomarker positivepopulation
The measure of interest is the HR of OS.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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 surgeryor definitive chemoradiation.

3. Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for anyother known genomic alteration for which there are locally approved targeted first-line therapies.

4. Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.

5. Known tumour PD-L1 expression status defined as TC>= 50%

6. At least one lesion, not previously irradiated that qualifies as a RECIST1.1 target lesion at baseline

7. ECOG performance status of 0 or 1

8. Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention

Exclude criteria

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, sarcomatoidvariant.

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, a
ctiveILD/pneumonitis, cardiac disease.

6. Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.

7. History of non-infectious ILD/pneumonitis that required steroids, hascurrent ILD/pneumonitis, or has suspected ILD/pneumonitis thatcannot be ruled out by imaging at screening

8. Has severe pulmonary function compromise resulting fromintercurrent pulmonary illnesses

9. Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and wh
o 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 infectionthat is not well controlled

13. History of active primary immunodeficiency

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06357533