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

Daiichi Sankyo

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: DS-3939a; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Carboplatin; Drug: DS-1103a

Study type: Interventional

Funder types: Industry

Identifiers

NCT07739966

DS3939-156

2026-525218-75-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Full description

The study includes 2 independent substudies, which have been defined by treatment combination and participant population as follows:

1. Substudy 1 will evaluate the safety and efficacy of DS-3939a in combination with immunotherapy with or without chemotherapy (carboplatin or pemetrexed) in participants with locally advanced unresectable or metastatic non-squamous (NSQ) NSCLC in the first-line setting.
2. Substudy 2 will evaluate the safety and efficacy of DS-3939a in combination with DS-1103a or as a monotherapy in participants with locally advanced unresectable or metastatic NSQ NSCLC who are pretreated.

Each sub study will be conducted in 2 parts: Dose escalation (Part 1) and Dose expansion (Part 2). The allocation of participants in Part 1 will be non-randomized, and in Part 2, it will be randomized for both substudies.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 10 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: DS-3939a

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

Active Comparator group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: Pemetrexed

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

Experimental group

Description:

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.

Treatment:

Drug: DS-1103a

Drug: DS-3939a

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

Experimental group

Description:

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.

Treatment:

Drug: DS-1103a

Drug: DS-3939a

Substudy 2: Part 2: DS-3939a

Active Comparator group

Description:

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.

Treatment:

Drug: DS-3939a