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

Phase 2Not Yet RecruitingNCT07739966

Daiichi Sankyo400 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

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

Interventions

DS-3939aDRUG

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

PembrolizumabDRUG

Pembrolizumab will be administered as an IV infusion.

CarboplatinDRUG

Carboplatin will be administered as an IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: Up to approximately 4 years

Secondary Outcomes

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

OR is defined as participants with a BOR of confirmed CR or confirmed PR as assessed by investigator per RECIST v1.1.

Time frame: Up to approximately 5 years

Part 2: Number of Participants With TEAEs

Central Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

9089926400 CTRinfo_us@daiichisankyo.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Pemetrexed will be administered as an IV infusion.

DS-1103aDRUG

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

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).

Time frame: Up to approximately 5 years

Parts 1 and 2: Duration of Response (DoR)

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.

Time frame: Up to approximately 5 years

Parts 1 and 2: Disease Control Rate (DCR)

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.

Time frame: Up to approximately 5 years

Parts 1 and 2: Time To Response (TTR)

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).

Time frame: Up to approximately 5 years

Parts 1 and 2: Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors

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.

Time frame: Up to approximately 5 years

Parts 1 and 2: Progression-Free Survival (PFS) Per RECIST v1.1 as Assessed by Investigator

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.

Time frame: Up to approximately 5 years

Parts 1 and 2: Overall Survival (OS)

OS is defined as the time from the first dose of any trial intervention(s) to death due to any cause.

Time frame: Up to approximately 5 years

Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a