A Study of DS-3939a in Participants With Solid Tumors

NCT07739966 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: DS3939-1562026-525218-75-00
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of the study is to evaluate the safety, tolerability, and efficacy of DS-3939a in combination with other anticancer agents or as a monotherapy in participants with solid tumors.

Conditions

Solid Tumor; Locally Advanced Non-Small Cell Lung Cancer; Metastatic Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)

  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.

  During first cycle (Cycle length=21 days)

• Part 1: Number of Participants With TEAEs

  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).

  Up to approximately 4 years

• Part 2: Objective Response (OR) Per RECIST v1.1 as Assessed by Investigator

  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.

  Up to approximately 4 years

Secondary Outcomes (20)

• Part 1: OR Per RECIST v1.1 as Assessed by Investigator

  Up to approximately 5 years

• Part 2: Number of Participants With TEAEs

  Up to approximately 5 years

• Parts 1 and 2: Duration of Response (DoR)

  Up to approximately 5 years

• Parts 1 and 2: Disease Control Rate (DCR)

  Up to approximately 5 years

• Parts 1 and 2: Time To Response (TTR)

  Up to approximately 5 years

Study Arms (10)

Substudy 1: Part 1: Cohort A: DS-3939a + Pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Substudy 1: Part 1: Cohort B: DS-3939a + Pembrolizumab + Carboplatin

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Carboplatin

Substudy 1: Part 1: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Pemetrexed

Substudy 1: Part 2: Cohort A: DS-3939a + Pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Substudy 1: Part 2: Cohort B: DS-3939a + Pembrolizumab + Carboplatin

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Carboplatin

Substudy 1: Part 2: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Pemetrexed

Substudy 1: Part 2: Cohort D: Pembrolizumab + Carboplatin + Pemetrexed

ACTIVE COMPARATOR

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: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed

Substudy 2: Part 1: DS-3939a + DS-1103a

EXPERIMENTAL

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; Drug: DS-1103a

Substudy 2: Part 2: DS-3939a + DS-1103a

EXPERIMENTAL

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; Drug: DS-1103a

Substudy 2: Part 2: DS-3939a

ACTIVE COMPARATOR

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

Interventions

DS-3939a DRUG

DS-3939a will be administered as an IV infusion.

Substudy 1: Part 1: Cohort A: DS-3939a + Pembrolizumab; Substudy 1: Part 1: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 1: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 1: Part 2: Cohort A: DS-3939a + Pembrolizumab; Substudy 1: Part 2: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 2: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 2: Part 1: DS-3939a + DS-1103a; Substudy 2: Part 2: DS-3939a; Substudy 2: Part 2: DS-3939a + DS-1103a

Pembrolizumab DRUG

Pembrolizumab will be administered as an IV infusion.

Also known as: MK-3475

Substudy 1: Part 1: Cohort A: DS-3939a + Pembrolizumab; Substudy 1: Part 1: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 1: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 1: Part 2: Cohort A: DS-3939a + Pembrolizumab; Substudy 1: Part 2: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 2: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 1: Part 2: Cohort D: Pembrolizumab + Carboplatin + Pemetrexed

Carboplatin DRUG

Carboplatin will be administered as an IV infusion.

Substudy 1: Part 1: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 2: Cohort B: DS-3939a + Pembrolizumab + Carboplatin; Substudy 1: Part 2: Cohort D: Pembrolizumab + Carboplatin + Pemetrexed

Pemetrexed DRUG

Pemetrexed will be administered as an IV infusion.

Substudy 1: Part 1: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 1: Part 2: Cohort C: DS-3939a + Pembrolizumab + Pemetrexed; Substudy 1: Part 2: Cohort D: Pembrolizumab + Carboplatin + Pemetrexed

DS-1103a DRUG

DS-1103a will be administered as an IV infusion.

Substudy 2: Part 1: DS-3939a + DS-1103a; Substudy 2: Part 2: DS-3939a + DS-1103a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign and date the Main Trial informed consent form (ICF), prior to the start of any trial-specific procedures.
• 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).
• Histologically documented Stage IIIB, IIIC disease who is not candidate for surgical resection or definitive chemoradiation, or Stage IV NSQ NSCLC.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 assessed no more than 14 days prior to initiation of trial interventions.
• Has adequate organ function.
• Participants must have measurable disease by investigator assessment according to RECIST v1.1.
• \. Participants must not have received prior systemic therapy for locally advanced unresectable or metastatic NSCLC.
• 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.
• 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
• Part 2 only: Participants must have received only 1 or 2 prior lines of anticancer therapy for the advanced disease setting.

You may not qualify if:

• Prior systemic anticancer therapy targeting MUC1 or TA-MUC1.
• Prior systemic anticancer therapy with topoisomerase 1 inhibitor or topoisomerase 1 inhibitor-based antibody-drug conjugate (ADCs) (e.g., datopotamab deruxtexan and Sacituzumab govitecan).
• Has spinal cord compression or clinically active central nervous system (CNS) metastases.
• Has multiple primary malignancies.
• 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
• Has active or uncontrolled human immunodeficiency virus (HIV) infection.
• Has active or uncontrolled hepatitis B virus (HBV)/hepatitis C virus (HCV) infection.
• Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
• Current participation in other therapeutic investigational procedures, except for participation in long term survival follow-up (LTSFU) without any investigational treatment.

Sponsors & Collaborators

• Daiichi Sankyo: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

9089926400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: July 31, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): January 29, 2032
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that have 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.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed 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.