A Phase 1b/2, Multicenter, 2-part, Open-label Trial to Evaluate DS-3939a in Participants With Solid Tumors
A Study of DS-3939a in Participants With Solid Tumors
Inoguchi Akihiro
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial_jp@daiichisankyo.com
Contact for Clinical Trial Information
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial_jp@daiichisankyo.com
Pending
Nov. 02, 2026
400
Interventional
non-randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1. Sign and date the Main Trial informed consent form (ICF), prior to the start of any trial-specific procedures.
2. Adults greater than or equal to (>=) 18 years of age at the time the Main Trial ICF is signed (follow local regulatory requirements if the legal age of consent for trial participation is >18 years old).
3. Histologically documented Stage IIIB, IIIC disease who is not candidate for surgical resection or definitive chemoradiation, or Stage IV NSQ NSCLC.
4. Has a left ventricular ejection fraction (LVEF) >=50 percent (%) by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days of the first trial intervention.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 assessed no more than 14 days prior to initiation of trial interventions.
6. Has adequate organ function.
7. Participants must have measurable disease by investigator assessment according to RECIST v1.1.
Additional Inclusion Criteria for Substudy 1:
1. Participants must not have received prior systemic therapy for locally advanced unresectable or metastatic NSCLC.
Additional Inclusion Criteria for Substudy 2:
1. Participants with AGA (excluding EGFR mutation): Participants have been previously treated with targeted therapy for the AGA and platinum-based chemotherapy for the advanced disease setting.
2. Participants without AGA: Participants have been previously treated with platinum-based chemotherapy and anti-programmed death-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibody.
3. Part 2 only: Participants must have received only 1 or 2 prior lines of anticancer therapy for the advanced disease setting.
1. Prior systemic anticancer therapy targeting MUC1 or TA-MUC1.
2. Prior systemic anticancer therapy with topoisomerase 1 inhibitor or topoisomerase 1 inhibitor-based antibody-drug conjugate (ADCs) (e.g., datopotamab deruxtexan and Sacituzumab govitecan).
3. Has spinal cord compression or clinically active central nervous system (CNS) metastases.
4. Has multiple primary malignancies.
5. Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening.
6. Has active or uncontrolled human immunodeficiency virus (HIV) infection.
7. Has active or uncontrolled hepatitis B virus (HBV)/hepatitis C virus (HCV) infection.
8. Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
9. Current participation in other therapeutic investigational procedures, except for participation in long term survival follow-up (LTSFU) without any investigational treatment.
Experimental: Substudy 1: Part 1: Cohort A: DS-3939a + Pembrolizumab
Participants will receive intravenous (IV) infusion of DS-3939a, every 3 weeks (Q3W) on Day 1 of each 21-day cycle until the time radiographic disease progression has been documented as assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator or other reason for treatment discontinuation has been met along with pembrolizumab, 200 milligrams (mg), Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles or until treatment discontinuation criteria are me.
Drug: DS-3939a, Pembrolizumab
Experimental: Substudy 1: Part 1: Cohort B: DS-3939a + Pembrolizumab + Carboplatin
Participants will receive IV infusion of DS-3939a, Q3W on Day 1 of each 21-day cycle until the time radiographic disease progression has been documented as assessed per RECIST v1.1 by investigator or other reason for treatment discontinuation has been met along with pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles and carboplatin at area under the curve (AUC) 5, Q3W on Day 1 of each 21-day cycle up to maximum of 4 cycles or until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab, Carboplatin
Experimental: Substudy 1: Part 1: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed
Participants will receive IV infusion of DS-3939a, Q3W on Day 1 of each 21-day cycle until the time radiographic disease progression has been documented as assessed per RECIST v1.1 by investigator or other reason for treatment discontinuation has been met along with pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles and pemetrexed 500 milligrams per meter square (mg/m^2), Q3W on Day 1 of each 21-day cycle until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab, Pemetrexed
Experimental: Substudy 1: Part 2: Cohort A: DS-3939a + Pembrolizumab
Participants will receive IV infusion of DS-3939a at the recommended dose for expansion (RDE) based on Part 1 data, along with pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles or until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab
Experimental: Substudy 1: Part 2: Cohort B: DS-3939a + Pembrolizumab + Carboplatin
Participants will receive IV infusion of DS-3939a at the RDE based on Part 1 data, along with pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles and carboplatin at AUC 5, Q3W on Day 1 of each 21-day cycle up to a maximum of 4 cycles or until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab, Carboplatin
Experimental: Substudy 1: Part 2: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed
Participants will receive IV infusion of DS-3939a at the RDE based on Part 1 data, along with pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles and pemetrexed 500 mg/m^2, Q3W on Day 1 of each 21-day cycle until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab, Pemetrexed
Active Comparator: Substudy 1: Part 2: Cohort D: Pembrolizumab + Carboplatin + Pemetrexed
Participants will receive IV infusions of pembrolizumab, 200 mg, Q3W on Day 1 of each 21-day cycle up to a maximum of 35 cycles, along with carboplatin at AUC 5, Q3W on Day 1 of each 21-day cycle up to maximum of 4 cycles and pemetrexed 500 mg/m^2, Q3W on Day 1 of each 21-day cycle until the discontinuation criteria are met.
Drug: DS-3939a, Pembrolizumab, Pemetrexed
Experimental: Substudy 2: Part 1: DS-3939a + DS-1103a
Participants will receive IV infusion of DS-3939a, along with DS-1103a, Q3W on Day 1 of each 21-day cycle until radiographic disease progression as assessed by investigator, or other reason for treatment discontinuation criteria are met.
Drug: DS-3939a, DS-1103a
Experimental: Substudy 2: Part 2: DS-3939a + DS-1103a
Participants will receive IV infusion of DS-3939a at the RDE based on Part 1 data, along with DS-1103a, Q3W on Day 1 of each 21-day cycle until radiographic disease progression as assessed by investigator, or other reason for treatment discontinuation criteria are met.
Drug: DS-3939a, DS-1103a
Active Comparator: Substudy 2: Part 2: DS-3939a
Participants will receive IV infusion of DS-3939a at the RDE based on Part 1 data, Q3W on Day 1 of each 21-day cycle until radiographic disease progression as assessed by investigator, or other reason for treatment discontinuation criteria are met.
Drug: DS-3939a
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
[Time Frame: During first cycle (Cycle length=21 days)]
DLT is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes, environmental factors, unrelated trauma, etc., that occurs during the DLT-evaluation Period (Day 1 to the end of Cycle 1) and is Grade >=3. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0.
Part 1: Number of Participants With TEAEs
[Time Frame: Up to approximately 4 years]
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as AEs with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 50 days after the last dose date of trial intervention, unless otherwise specified in the applicable sub-study protocol).
Part 2: Objective Response (OR) Per RECIST v1.1 as Assessed by Investigator
[Time Frame: Up to approximately 4 years]
OR is defined as participants with a best overall response (BOR) of confirmed response (CR) or confirmed partial response (PR) as assessed by investigator per RECIST v1.1.
1. Part 1: OR Per RECIST v1.1 as Assessed by Investigator
[Time Frame: Up to approximately 5 years]
OR is defined as participants with a BOR of confirmed CR or confirmed PR as assessed by investigator per RECIST v1.1.
2. Part 2: Number of Participants With TEAEs
[Time Frame: Up to approximately 5 years]
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as AEs with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 50 days after the last dose date of trial intervention, unless otherwise specified in the applicable sub-study protocol).
3. Parts 1 and 2: Duration of Response (DoR)
[Time Frame: Up to approximately 5 years]
DoR is defined as the time (month) from date of initial response (CR or PR) to the earlier date of the first objective documentation of radiographic disease progression or death due to any cause.
4. Parts 1 and 2: Disease Control Rate (DCR)
[Time Frame: Up to approximately 5 years]
Disease control is defined as participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) per RECIST v1.1. DCR is defined as the percentage of participants with disease control.
5. Parts 1 and 2: Time To Response (TTR)
[Time Frame: Up to approximately 5 years]
TTR is defined as the time (month) from the first dose of any trial intervention(s) to the date of the first documentation of objective response in responders (BOR of confirmed CR or confirmed PR).
6. Parts 1 and 2: Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors
[Time Frame: Up to approximately 5 years]
The best percentage change in SoD is defined as the percentage change in the smallest SoD from all postbaseline tumor assessments, taking as reference the baseline SoD. SoD is the sum of diameters from all measurable target lesions.
7. Parts 1 and 2: Progression-Free Survival (PFS) Per RECIST v1.1 as Assessed by Investigator
[Time Frame: Up to approximately 5 years]
PFS is defined as the time (month) from the first dose of any trial intervention(s) to the earlier date of the first objective documentation of radiographic disease progression as assessed by investigator per RECIST v1.1 or death due to any cause.
8. Parts 1 and 2: Overall Survival (OS)
[Time Frame: Up to approximately 5 years]
OS is defined as the time from the first dose of any trial intervention(s) to death due to any cause.
9. Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
10. Parts 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
11. Parts 1 and 2: Area Under the Plasma Concentration-time Curve up to the Last Quantifiable Time (AUClast) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
12. Parts 1 and 2: Area Under the Concentration-time Curve up to Time Tau (AUCtau) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
13. Parts 1 and 2: Trough Concentration (Ctrough) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
14. Parts 1 and 2: Percentage of Participants With Positive Anti-Drug Antibody (ADA) Against DS-3939a
[Time Frame: Up to approximately 5 years]
15. Substudy 2: AUClast of DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
16. Substudy 2: AUCtau of DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
17. Substudy 2: Cmax of DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
18. Substudy 2: Tmax of DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
19. Substudy 2: Ctrough of DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days)]
20. Substudy 2: Percentage of Participants With Positive ADA for DS-1103a Dosed in Combination With DS-3939a
[Time Frame: Up to approximately 5 years]
Daiichi Sankyo Co., Ltd.
TBD
TBD, Tokyo
Yes
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Supporting Information:
-Study Protocol
-Statistical Analysis Plan (SAP)
-Informed Consent Form (ICF)
Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and 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.
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URL: https://vivli.org/ourmember/daiichi-sankyo/
