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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04484142

Collaborator

AstraZeneca (Industry)

137

Enrollment

Locations

Arm

37.3

Anticipated Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: DS-1062a	Phase 2

Detailed Description

This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC with actionable genomic alterations and who have been previously been treated with 1 platinum-containing therapy and 1 or more lines of targeted therapy. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all participants either have been followed for at least 9 months after the start of study treatment or have discontinued from the study, whichever occurs first.

Study Design

Study Type:

Interventional

Actual Enrollment :

137 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Mar 30, 2021

Anticipated Primary Completion Date :

Mar 7, 2023

Anticipated Study Completion Date :

May 9, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-1062a 6.0 mg/kg Participants will receive 6.0 mg/kg of DS-1062a	Drug: DS-1062a DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks Other Names: Datopotamab Deruxtecan

Arm

Intervention/Treatment

Experimental: DS-1062a 6.0 mg/kg

Participants will receive 6.0 mg/kg of DS-1062a

Drug: DS-1062a

DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Other Names:

Datopotamab Deruxtecan

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) As Assessed by Blind Independent Central Review Per RECIST v1.1 Following DS-1062a Intravenous Infusion [From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months]
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.

Secondary Outcome Measures

Duration of Response (DOR) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous Infusion [From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months]
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.
Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous (IV) Infusion [From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months]
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.
Overall Survival (OS) Following DS-1062a Intravenous Infusion [From baseline until death due to any cause, up to approximately 23 months]
OS is defined as the time from the start of study treatment to the date of death due to any cause.
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 [From baseline up to approximately 23 months post treatment]
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.
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a [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)]
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a [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)]
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a [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)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria for this study.

Sign and date the inform consent form (ICF) prior to the start of any study- specific 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:

Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
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 the most recent treatment regimen for advanced or metastatic NSCLC.
Participant must meet the following for advanced or metastatic NSCLC:

Has been treated with at least one but no more than two cytotoxic agent-containing therapy in the metastatic setting:

One platinum-containing regimen (either as monotherapy or combination therapy).
May have received up to one additional line of cytotoxic agent-containing therapy.
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.

May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent).
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:

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.
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 × 4 micron sections or a tissue block equivalent of 10 × 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.

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study.

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:

Any chemotherapeutic agent targeting topoisomerase I, including antibody drug conjugate (ADC) containing such agent.
TROP2-targeted therapy.

Uncontrolled or significant cardiovascular disease:

History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
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 scan within 28 days of Cycle 1 Day 1) in order to be eligible.
History of serious cardiac arrhythmia requiring treatment.
LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.
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 non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85259
2	University of California San Diego	La Jolla	California	United States	92093
3	UCLA	Santa Monica	California	United States	90404
4	Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
5	Sarah Cannon Research Institute at Florida Cancer Center, North	Gainesville	Florida	United States	32605
6	Mayo Clinic	Jacksonville	Florida	United States	32224
7	AdventHealth Orlando	Orlando	Florida	United States	32804
8	Sarah Cannon Research Institute at Florida Cancer Center, South	Port Charlotte	Florida	United States	33980
9	Moffitt Cancer Center	Tampa	Florida	United States	33612
10	The Office of Dr. Frederick P. Smith MD	Chevy Chase	Maryland	United States	20815
11	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
13	University of Michigan	Detroit	Michigan	United States	48202
14	Mayo Clinic	Rochester	Minnesota	United States	55905
15	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
16	XCancer / Regional Cancer Care Associate (Astera)	East Brunswick	New Jersey	United States	08816
17	NYU Langone Medical Center	New York	New York	United States	10016
18	Weill Cornell Medical College	New York	New York	United States	10065
19	New York Cancer and Blood Specialists	Port Jefferson	New York	United States	11776
20	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
21	Avera Cancer Institute Sioux Falls	Sioux Falls	South Dakota	United States	57105
22	Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga	Chattanooga	Tennessee	United States	37404
23	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
24	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
25	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
26	Virginia Cancer Specialists	Athens	Virginia	United States	30607
27	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
28	Seattle Cancer Care Alliance	Seattle	Washington	United States	33612
29	APHM - Hopital Nord	Marseille Cedex 20	Bouches-Du-RhÃ´ne	France	13015
30	Gustav Roussy Cancer Campus Grand Paris	Villejuif	ile-de-France	France	94805
31	University Hospital of Nantes	Nantes	Loire-Atlantique	France	44000
32	CHU Toulouse Hopital Larrey	Toulouse	Occitanie	France	31059
33	Centre Leon Berard	Lyon	Rhone	France	69008
34	Institut Curie	Paris		France	75005
35	Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil	Strasbourg		France	67091
36	Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse	Toulon		France	83000
37	Thoraxklinik Heidelberg	Heidelberg	Baden-Württemberg	Germany	69126
38	Asklepios Fachklinik Muenchen-Gauting	Gauting	Bayern	Germany	82131
39	IKF Krankenhaus Nordwest	Frankfurt Am Main	Hessen	Germany	60488
40	Universitaet zu Koeln - Uniklinik Koeln	Koeln	North Rhine-Westphal	Germany	50937
41	Medizinische Hochschule Hannover	Hannover		Germany	30625
42	Thoraxklinik Heidelberg gGmbH	Heidelberg		Germany	69126
43	National Koranyi Institute for TB and Pulmonology	Budapest		Hungary	H-1121
44	Pulmonology Hospital Törökbálint	Torokbalint		Hungary	H-2045
45	Azienda Ospedaliera Universitaria Policlinico-OVE	Catania	CT	Italy	95030
46	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	RM	Italy	00168
47	University of Turin San Luigi Hospital	Orbassano	Torino	Italy	10043
48	Azienda Ospedaliero-Universitaria S. Orsola Malpighi	Bologna		Italy	40138
49	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
50	Istituto Europeo di Oncologia	Milano		Italy	20141
51	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43126
52	Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS	Reggio Emilia		Italy	42123
53	Fujita Health University Hospital	Toyoake-shi	Aichi	Japan	470-1192
54	National Cancer Center Hospital East	Kashiwa-shi	Chiba	Japan	277-8577
55	Hokkaido Cancer Center	Sapporo-shi	Hokkaido	Japan	003-0804
56	Kyoto University Hospital	Kyoto-shi	Kyoto	Japan	606-8507
57	Niigata Cancer Center Hospital	Niigata-shi	Niigata	Japan	961-8566
58	Kansai Medical University Hospital	Hirakata-shi	Osaka	Japan	573-1191
59	Osaka City General Hospital	Osaka-shi	Osaka	Japan	534-0021
60	Osaka International Cancer Institute	Osaka-shi	Osaka	Japan	541-8567
61	Kindai University Hospital	Ōsaka-sayama	Osaka	Japan	589-8511
62	Shizuoka Cancer Center	Nagaizumi-chō	Shizuoka	Japan	411-8777
63	Tokushima University Hospital	Tokushima-shi	Tokushima	Japan	770-8503
64	National Cancer Center Hospital	Chuo Ku	Tokyo	Japan	104-0045
65	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo	Japan	135-8550
66	Aichi Cancer Center Hospital	Aichi		Japan	464-8681
67	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do	Korea, Republic of	110744
68	Seoul National University Hospital	Seoul		Korea, Republic of	03080
69	Severance Hospital	Seoul		Korea, Republic of	03722
70	Asan Medical Center	Seoul		Korea, Republic of	05505
71	Samsung Medical Center	Seoul		Korea, Republic of	6273
72	The Netherlands Cancer Institute	Amsterdam	North Holland	Netherlands	1066 CX
73	Erasmus MC	Rotterdam	Zuid Holland	Netherlands	3015 CD
74	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda	Madrid	Spain	28222
75	Hospital Regional Universitario Malaga	Málaga	Malaga	Spain	29010
76	Hospital General Universitario de Alicante	Alicante		Spain	03010
77	Hospital Universitario Vall dHebron	Barcelona		Spain	08035
78	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
79	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
80	National Cheng Kung University Hospital	Tainan		Taiwan	70403
81	Taipei Veterans General Hospital	Taipei City		Taiwan	11217
82	National Taiwan University Hospital NTUH	Taipei		Taiwan	100
83	Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan	112