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Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum-based Chemotherapy (TROPION-Lung05)

Phase 2 Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations (TROPION-Lung05)

Inoguchi Akihiro

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Not Recruiting

Feb. 15, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Sign and date the inform consent form (ICF) prior to the start of any studyspecific qualification procedures.
- Adults >=18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)
- Has pathologically documented NSCLC that:
a. Has stage IIIB, IIIC or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
b. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
*KRAS mutations in the absence of any of the genomic alterations specified above will be excluded.
**Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for enrollment.
***Participants who have not received osimertinib should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase inhibitor (TKI), unless the participant is already known to be positive with document results for this mutation or unless osimertinib is not locally approved.
- Has documentation of radiographic disease progression while on or after receiving themost recent treatment regimen for advanced or metastatic NSCLC.
- Participant must meet the following for advanced or metastatic NSCLC:
a. Has been treated with at least one but no more than two cytotoxic agent containing therapy in the metastatic setting:
i. One platinum-containing regimen (either as monotherapy or combination therapy).
ii. May have received up to one additional line of cytotoxic agent-containing therapy.
iii. Those who received a platinum-containing regimen as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
b. May have received up to one checkpoint inhibitor (CPI)-containing regimen (maybe in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent).
c. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally approved for the participant's applicable genomic alteration at the time of screening:
i. Those who received a targeted agent for the applicable genomic alterations in the study as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alterations (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
ii. Participants who have been treated with a prior TKI must receive additional targeted therapy, if clinically appropriate, for the genomic alterations that are considered amenable or the participant will not be allowed in the study.
- Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 x 4 micron sections or a tissue block equivalent of 10 x 4 micron sections may be substituted for the mandatory biopsy collected during screening.
- Measurable disease based on local imaging assessment using RECIST v1.1.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

- 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. Participants with clinically inactive brain metastases may be included in the study.
- Has leptomeningeal carcinomatosis.
- Has prior treatment with:
a. Any chemotherapeutic agent targeting topoisomerase I, including ADC containing such agent.
b. TROP2-targeted therapy.
- Uncontrolled or significant cardiovascular disease:
a. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
b. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
c. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening. Participants with a history of Class II to IV CHF prior to screening must have returned to Class I CHF and have LVEF >=50% (by either an ECHO or MUGA scanwithin 28 days of Cycle 1 Day 1) in order to be eligible.
d. History of serious cardiac arrhythmia requiring treatment.
e. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.
f. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).
- 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.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
- Clinically significant corneal disease.
- Has other primary malignancies, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for >=3 years.

Both

Advanced or Metastatic NSCLC

Participants will receive 6.0 mg/kg of DS-1062a
DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

1. Objective Response Rate (ORR) As Assessed by Blind Independent Central Review Per RECIST v1.1 Following DS-1062a Intravenous Infusion
ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.
[Time Frame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months]

1.Duration of Response (DOR) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous Infusion
DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.
[ Time Frame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months ]
2.Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous (IV) Infusion PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of progressive disease or death due to any cause.
[ Time Frame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months ]
3.Overall Survival (OS) Following DS-1062a Intravenous Infusion
OS is defined as the time from the start of study treatment to the date of death due to any cause.
[ Time Frame: From baseline until death due to any cause, up to approximately 23 months ]
4.Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Intravenous Infusion in Participants with Advanced or Metastatic NSCLC with Actionable Genomic Alterations
Reported treatment-emergent adverse events, serious adverse events, adverse events of interest, and those considered related to the study drug or study procedures, or that associated DS-1062a reduction, interruption, or discontinuation.
[Time Frame: From baseline up to approximately 23 months post treatment ]
5.Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
[ Time Frame: Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days) ]
6.Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
[ Time Frame: Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days) ]
7.Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for DS-1062, total Anti-TROP2 antibody, and MAAA-1181a.
[Time Frame: Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days) ]

+81-562-93-2111

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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 Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report 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/

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