Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Non-Small Cell Lung Cancer Clinical Trial

— TROPION-Lung10  

Official title:

A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations (TROPION-Lung10)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06357533
• Other study ID #: D7632C00001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 26, 2024
• Est. completion date: May 24, 2030

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Description:

This is a Phase III, randomized, open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig monotherapy versus Pembrolizumab monotherapy for the first-line treatment of participants with locally-advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 675
• Est. completion date: May 24, 2030
• Est. primary completion date: May 24, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented non-squamous NSCLC.
• 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.
• Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved targeted first-line therapies.
• Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.
• Known tumour PD-L1 expression status defined as TC = 50%
• At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline
• ECOG performance status of 0 or 1
• Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention

Exclusion Criteria:

• Prior systemic therapy for advanced/metastatic NSCLC.
• Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
• History of another primary malignancy within 3 years
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
• Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
• 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
• Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses
• Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
• History of leptomeningeal carcinomatosis
• Known clinically significant corneal disease
• Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
• History of active primary immunodeficiency

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Datopotamab Deruxtecan
Datopotamab Deruxtecan IV (intravenous)
• Rilvegostomig
Rilvegostomig IV (intravenous)
• Pembrolizumab
Pembrolizumab IV (intravenous)

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Melbourne
Australia	Research Site	South Brisbane
Austria	Research Site	Innsbruck
Austria	Research Site	Krems
Austria	Research Site	Linz
Austria	Research Site	Rankweil
Austria	Research Site	Wien
Austria	Research Site	Wien
Brazil	Research Site	Rio de Janeiro
Canada	Research Site	Chicoutimi
Canada	Research Site	Lévis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivieres	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Winnipeg	Manitoba
Germany	Research Site	Gauting
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Gyula
Hungary	Research Site	Kecskemét
Hungary	Research Site	Salgótarján
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Szekszárd
Hungary	Research Site	Törökbálint
Italy	Research Site	Bergamo
Italy	Research Site	Genoa
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Padova
Italy	Research Site	Pavia
Italy	Research Site	Ravenna
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Tokushima-shi
Japan	Research Site	Utsunomiya-shi
Korea, Republic of	Research Site	Changwon
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Suwon-si
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Jerez de la Frontera
Spain	Research Site	Reus,Tarragona
Spain	Research Site	Salamanca
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adapazari
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Diyarbakir
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
United Kingdom	Research Site	Inverness
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Truro

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

Australia,  Austria,  Brazil,  Canada,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) in TROP2 biomarker positive participants.	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: • TROP2 biomarker positive population; The measure of interest is the HR of PFS. PFS by investigator will be reported as a sensitivity analysis.	Approximately 4 years
Primary	Overall Survival (OS) in TROP2 biomarker positive participants.	OS is defined as the time from randomisation until the date of death due to any cause.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of OS.	Approximately 6 years
Secondary	Progression-Free Survival (PFS) in the intent-to-treat (ITT) population.	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: • ITT population; The measure of interest is the HR of PFS. PFS by investigator will be reported as a sensitivity analysis.	Approximately 4 years
Secondary	Overall Survival (OS) in the intent-to-treat (ITT) population.	OS is defined as the time from randomisation until the date of death due to any cause.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: • ITT population The measure of interest is the HR of OS.	Approximately 6 years
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a CR or PR, as determined by BICR per RECIST 1.1.; The analyses will include all randomised participants, as randomised, with measurable disease at baseline, in the following populations: TROP2 biomarker positive population; ITT population Data obtained from randomisation up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who go off treatment without a response or progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR.; The measure of interest is the OR of the ORR. ORR by investigator will be reported as a sensitivity analysis.	Approximately 4 years
Secondary	Duration of Response (DoR)	DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator assessment or death due to any cause.; The analyses will include all randomised participants who have a response, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following populations: TROP2 biomarker positive population; ITT population The measure of interest is the median of DoR. DoR by investigator will be reported as a sensitivity analysis.	Approximately 4 years
Secondary	Participant-reported lung cancer symptoms of NSCLC in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.	Time to deterioration in pulmonary symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ.; Time to deterioration in overall lung cancer symptoms as measured by the NSCLC-SAQ.; Time to deterioration is defined as the time from randomisation until the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analyses will include all randomised participants, in the following populations: TROP2 biomarker positive population; ITT population The measure of interest is the HR of time to deterioration in pulmonary symptoms and the HR of time to deterioration in overall lung cancer symptoms.	Approximately 6 years
Secondary	Participant-reported physical functioning in participants treated with Dato DXd in combination with rilvegostomig relative to pembrolizumab.	Time to deterioration in physical functioning as measured by PROMIS Physical Function short form 8c.; Time to deterioration is defined as the time from randomisation until the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analyses will include all randomised participants, in the following populations: TROP2 biomarker positive population; ITT population The measure of interest is the HR of time to deterioration in physical functioning.	Approximately 6 years
Secondary	Participant-reported GHS/QoL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.	Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.; Time to deterioration is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants, in the following populations: TROP2 biomarker positive population; ITT population The measure of interest is the HR of time to deterioration in GHS/QoL.	Approximately 6 years
Secondary	Pharmacokinetics (PK)	Concentration of rilvegostomig, Dato-DXd, total anti TROP2 antibody, and MAAA 1181a (payload deruxtecan) in plasma or serum and PK parameters (peak and trough concentrations).	Approximately 6 years
Secondary	Immunogenicity	Presence of ADA for Dato-DXd and rilvegostomig (confirmatory results, titres and neutralising antibodies for confirmed positive samples).	Approximately 6 years
Secondary	Second Progression-Free Survival (PFS2).	PFS2 is defined as the time from randomisation to the earliest of the progression events (following the initial progression), subsequent to first subsequent therapy, or death. Progression event includes radiological (RECIST 1.1) or clinical disease progression.; The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard practice.; The analyses will include all randomised participants, as randomised, regardless of whether the participant withdraws from subsequent therapy and regardless of missed visits, in the following populations: TROP2 biomarker positive population; ITT population The measure of interest is the HR of PFS2.	Approximately 6 years