Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)
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|ClinicalTrials.gov Identifier: NCT04526691|
Recruitment Status : Recruiting
First Posted : August 26, 2020
Last Update Posted : October 7, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Advanced or Metastatic NSCLC||Drug: Datopotamab deruxtecan Drug: Pembrolizumab Drug: Carboplatin Drug: Cisplatin||Phase 1|
The primary objective of this study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without 4 cycles of platinum chemotherapy in participants with advanced or metastatic NSCLC who have either been previously treated or are treatment naïve in a metastatic setting.
Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with 200 mg fixed-dose pembrolizumab in 6 study cohorts. This study will be conducted sequentially and dose escalation will occur according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0 mg/kg) and from 2-drug combination (Dato-DXd and pembrolizumab) to 3-drug combination regimen (Dato-DXd, pembrolizumab, and carboplatin or cisplatin).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose escalation and dose expansion model|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b, Multicenter, Open-label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)|
|Actual Study Start Date :||September 15, 2020|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||October 1, 2024|
Experimental: Datopotamab deruxtecan (Dato-DXd)
Dose Escalation and Dose Expansion: Datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic NSCLC
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (starting datopotamab deruxtecan dose of 4.0 mg/kg)
Other Name: Dato-DXd
Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W)
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m^2)
- Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Cycle 1 (Days 1 to 21) for DLTs and up to 28 days after last dose for TEAEs, up to approximately 30 months post-dose ]
- Objective Response Rate [ Time Frame: Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose ]
- Duration of Response [ Time Frame: From first objective response (confirmed CR or PR) to PD or death (whichever occurs first), up to approximately 30 months post-dose ]
- Progression-free Survival [ Time Frame: Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose ]
- Overall Survival [ Time Frame: Baseline up to death (any cause), up to approximately 30 months post-dose ]
- Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a [ Time Frame: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days) ]
- Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a [ Time Frame: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days) ]
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a [ Time Frame: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days) ]Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.
- Anti-drug Antibodies for Dato-DXd and Pembrolizumab [ Time Frame: Baseline up to approximately 30 months post-dose ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Histologically confirmed at diagnosis of NSCLC that:
- Is advanced or metastatic.
- Participants with non-squamous histology must have documented negative test results for actionable EGFR and ALK genomic alterations. Participants with squamous histology are required to undergo testing for EGFR and ALK genomic alterations if they are nonsmokers or under the age of 40 years.
- Has either documented negative or unknown test results for actionable genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver kinases.
- Participants with tumors that harbor KRAS mutations are eligible for this study.
- Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other kinases are eligible for the study.
- Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC.
Must meet the following prior therapy requirements for advanced or metastatic NSCLC:
- Dose escalation (all cohorts): Has received ≤2 lines of prior anticancer therapy for locally advanced or metastatic NSCLC.
- Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4 directed immunotherapy and may or may not have been treated with systemic chemotherapy for advanced or metastatic NSCLC.
- Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2): Has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC.
- Willing and able to undergo a mandatory tumor biopsy.
- Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers.
- Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1.
- Is not a candidate for surgical resection or chemoradiation with curative intent.
- Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Received a live vaccine within 30 days prior to the first dose of study treatment.
- Active, known, or suspected autoimmune disease.
- Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications, except for managing AEs.
- Prior organ transplantation, including allogeneic tissue or solid organ transplantation.
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- 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.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
History of another primary malignancy (beyond NSCLC) except for:
- Malignancy treated with curative intent and with no known active disease for ≥3 years.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526691
|Contact: (US & EU 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)||email@example.com|
|Study Director:||Global Clinical Leader||Daiichi Sankyo, Inc.|
|Responsible Party:||Daiichi Sankyo, Inc.|
|Other Study ID Numbers:||
2020-006047-25 ( EudraCT Number )
jRCT2031200193 ( Other Identifier: JAPIC )
KEYNOTE KN-B43 ( Other Identifier: Merck )
|First Posted:||August 26, 2020 Key Record Dates|
|Last Update Posted:||October 7, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (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/|
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
|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.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Advanced or Metastatic NSCLC
Datopotamab deruxtecan (Dato-DXd)
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Antineoplastic Agents, Immunological