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 (TROPION-Lung10)

• ClinicalTrials.gov Identifier: NCT06357533
• Recruitment Status: Recruiting
• First Posted: April 10, 2024
• Last Update Posted: May 16, 2024
• Sponsor: AstraZeneca
• Collaborator: Daiichi Sankyo
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: April 5, 2024
• First Posted Date: April 10, 2024
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: April 11, 2024
• Estimated Primary Completion Date: April 24, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2024)

• Progression-Free Survival (PFS) in TROP2 biomarker positive participants. [ Time Frame: Approximately 4 years ]
  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.
• Overall Survival (OS) in TROP2 biomarker positive participants. [ Time Frame: Approximately 6 years ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 5, 2024)

• Progression-Free Survival (PFS) in the intent-to-treat (ITT) population. [ Time Frame: Approximately 4 years ]
  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.
• Overall Survival (OS) in the intent-to-treat (ITT) population. [ Time Frame: Approximately 6 years ]
  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.
• Objective Response Rate (ORR) [ Time Frame: Approximately 4 years ]
  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.
• Duration of Response (DoR) [ Time Frame: Approximately 4 years ]
  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.
• Participant-reported lung cancer symptoms of NSCLC in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab. [ Time Frame: Approximately 6 years ]
  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.
• Participant-reported physical functioning in participants treated with Dato DXd in combination with rilvegostomig relative to pembrolizumab. [ Time Frame: Approximately 6 years ]
  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.
• Participant-reported GHS/QoL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab. [ Time Frame: Approximately 6 years ]
  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.
• Pharmacokinetics (PK) [ Time Frame: Approximately 6 years ]
  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).
• Immunogenicity [ Time Frame: Approximately 6 years ]
  Presence of ADA for Dato-DXd and rilvegostomig (confirmatory results, titres and neutralising antibodies for confirmed positive samples).
• Second Progression-Free Survival (PFS2). [ Time Frame: Approximately 6 years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Parallel Assignment

Masking: Single (Outcomes Assessor)
Masking Description:

Open-label, sponsor-blinded

Primary Purpose: Treatment

• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Datopotamab Deruxtecan
  Datopotamab Deruxtecan IV (intravenous)
  Other Name: Dato-DXd
• Drug: Rilvegostomig
  Rilvegostomig IV (intravenous)
  Other Name: AZD2936
• Drug: Pembrolizumab
  Pembrolizumab IV (intravenous)
  Other Name: KEYTRUDA

Study Arms

• Experimental: Arm 1: Dato-DXd in Combination With Rilvegostomig
  Participants in the Dato-DXd in combination with Rilvegostomig group will receive Dato-DXd plus rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
  Interventions:

  • Drug: Datopotamab Deruxtecan
  • Drug: Rilvegostomig
• Experimental: Arm 2: Rilvegostomig Monotherapy
  Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
  Intervention: Drug: Rilvegostomig
• Active Comparator: Arm 3: Pembrolizumab Monotherapy
  Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
  Intervention: Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 5, 2024): 675
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 9, 2030
• Estimated Primary Completion Date: April 24, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Poland, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT06357533
• Other Study ID Numbers: D7632C00001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)

Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.

For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool .

Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Daiichi Sankyo

Investigators

• Principal Investigator: Suresh S. Ramalingam, MD; Emory University, Atlanta, Georgia, United States of America.

• PRS Account: AstraZeneca
• Verification Date: May 2024