Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)

• ClinicalTrials.gov Identifier: NCT05555732
• Recruitment Status: Recruiting
• First Posted: September 27, 2022
• Last Update Posted: March 3, 2023
• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: AstraZeneca; Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Tracking Information

• First Submitted Date: September 22, 2022
• First Posted Date: September 27, 2022
• Last Update Posted Date: March 3, 2023
• Actual Study Start Date: January 11, 2023
• Estimated Primary Completion Date: August 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2022)

• Progression-free Survival Based on Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 29 months ]
  Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
• Overall Survival in Participants in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 57 months ]
  Overall Survival (OS) is defined as the time from randomization to death due to any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 22, 2022)

• Objective Response Rate by Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 29 months ]
  Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1.
• Progression-free Survival by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 29 months ]
  Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1.
• Objective Response Rate by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 29 months ]
  Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by the Investigator per RECIST Version 1.1.
• Duration of Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 29 months ]
  Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1.
• Time to Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization to date of first objective response (CR or PR), up to approximately 29 months ]
  Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1.
• Disease Control Rate by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 29 months ]
  Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1.
• Progression-free Survival 2 in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 57 months ]
  Progression-free Survival 2 (PFS2) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by local standard clinical practice
• Time to Deterioration in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 57 months ]
  Time to Deterioration (TTD) is defined as the time from randomization to first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13).
• Number of Participants With Treatment-emergent Adverse Events (TEAE) in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) [ Time Frame: Up to 57 months ]
  A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment.
• Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA [ Time Frame: Baseline and up to 57 months ]
  The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.

• 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: Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)
• Official Title: A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)
• Brief Summary: This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

Detailed Description

The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS <50% and advanced or metastatic NSCLC without actionable genomic alternations.

Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Non Small Cell Lung Cancer

Intervention

• Drug: Datopotamab Deruxtecan
  Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
  Other Name: Dato-DXd
• Drug: Pembrolizumab
  Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
  Other Name: Keytruda
• Drug: Pemetrexed
  Pemetrexed will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
  Other Names:

  • Alimta
  • Pemfexy
• Drug: Carboplatin
  Carboplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
• Drug: Cisplatin
  Cisplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Study Arms

• Experimental: Dato-DXd + Pembrolizumab + Platinum Chemotherapy
  Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
  Interventions:

  • Drug: Datopotamab Deruxtecan
  • Drug: Pembrolizumab
  • Drug: Carboplatin
  • Drug: Cisplatin
• Experimental: Dato-DXd + Pembrolizumab
  Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab.
  Interventions:

  • Drug: Datopotamab Deruxtecan
  • Drug: Pembrolizumab
• Active Comparator: Pembrolizumab + Pemetrexed + Platinum Chemotherapy
  Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Pemetrexed
  • Drug: Carboplatin
  • Drug: Cisplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 22, 2022): 975
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2027
• Estimated Primary Completion Date: August 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Sign and date the Main Informed Consent Form (ICF), prior to the start of any study- specific qualification procedures.
• Adults ≥18 at the time the Main ICF is signed.
• Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing.
• Has provided a formalin-fixed tumor tissue sample for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers.
• Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC.
• Has measurable disease based on local imaging assessment using RECIST v1.1.

• Histologically documented NSCLC that meets all of the following criteria:

  • Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition).
  • Documented negative test results for epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations based on analysis of tumor tissue.
  • No known actionable genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), or other actionable driver kinases with locally approved therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
• Has an adequate treatment washout period before Cycle 1 Day 1.
• Is willing and able to participate in the collection of patient-reported outcomes (PRO) data.

Exclusion Criteria:

• Has received prior systemic treatment for advanced/metastatic NSCLC.

• Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:

  • Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
  • TROP2-targeted therapy.
  • Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti-PD-ligand 2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
  • Any other immune checkpoint inhibitors.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
• Has spinal cord compression or clinically active untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Uncontrolled or significant cardiovascular disease, including:

  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex.
  • Myocardial infarction within 6 months prior to randomization.
  • Uncontrolled angina pectoris within 6 months prior to randomization.
  • LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
  • New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
  • Uncontrolled hypertension within 28 days before randomization.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.

• History of another primary malignancy (beyond NSCLC) except for:

  • Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study treatment and of low potential risk for recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression.
• Has a history of severe hypersensitivity reactions to either the drugs or inactive ingredients of Dato-DXd, pembrolizumab, carboplatin, cisplatin or pemetrexed.
• Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Has known human immunodeficiency virus (HIV) infection that is not well controlled.
• Has active or uncontrolled hepatitis B or C infection.
• Female who is pregnant or breastfeeding or intends to become pregnant.
• Any other medical conditions, including cardiac disease or psychological disorders, and/or substance abuse.
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has active, known, or suspected autoimmune disease.
• Has clinically significant corneal disease.
• Has had an allogeneic tissue/solid organ transplantation.
• Has received prior radiotherapy ≤4 weeks of start of study intervention or more than 30 Gy to the lung within 6 months of Cycle 1 Day 1.

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information; 908-992-6400; CTRinfo@dsi.com

Contact: (Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information; +81-3-6225-1111(M-F 9-5 JST); dsclinicaltrial@daiichisankyo.co.jp

• Listed Location Countries: Japan, Taiwan, United States

Administrative Information

• NCT Number: NCT05555732
• Other Study ID Numbers: DS1062-A-U303; 2022-500802-16 ( EudraCT Number )
• 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: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Current Responsible Party: Daiichi Sankyo, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo, Inc.
• Original Study Sponsor: Same as current

Collaborators

• AstraZeneca
• Merck Sharp & Dohme LLC

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

• PRS Account: Daiichi Sankyo, Inc.
• Verification Date: March 2023