Solid Tumor, Locally Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer
Conditions
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.
Detailed 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.
Interventions
DRUGDS-3939a
DS-3939a will be administered as an IV infusion.
DRUGPembrolizumab
Pembrolizumab will be administered as an IV infusion.
DRUGCarboplatin
Carboplatin will be administered as an IV infusion.
DRUGPemetrexed
Pemetrexed will be administered as an IV infusion.
DRUGDS-1103a
DS-1103a will be administered as an IV infusion.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: OR Per RECIST v1.1 as Assessed by Investigator | 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. |
| Part 2: Number of Participants With TEAEs | 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). |
| Parts 1 and 2: Duration of Response (DoR) | 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. |
| Parts 1 and 2: Disease Control Rate (DCR) | 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. |
| Parts 1 and 2: Time To Response (TTR) | 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). |
| Parts 1 and 2: Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors | 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. |
| Parts 1 and 2: Progression-Free Survival (PFS) Per RECIST v1.1 as Assessed by Investigator | 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. |
| Parts 1 and 2: Overall Survival (OS) | 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. |
| Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| 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 | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| 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 | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| 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 | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Parts 1 and 2: Trough Concentration (Ctrough) of Anti-TA-MUC1-ac-DXd, Total Anti-TA-MUC1 Antibody and MAAA-1181a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Parts 1 and 2: Percentage of Participants With Positive Anti-Drug Antibody (ADA) Against DS-3939a | Up to approximately 5 years | — |
| Substudy 2: AUClast of DS-1103a Dosed in Combination With DS-3939a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Substudy 2: AUCtau of DS-1103a Dosed in Combination With DS-3939a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Substudy 2: Cmax of DS-1103a Dosed in Combination With DS-3939a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Substudy 2: Tmax of DS-1103a Dosed in Combination With DS-3939a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Substudy 2: Ctrough of DS-1103a Dosed in Combination With DS-3939a | Pre-dose and post-dose at multiple timepoints during each cycle, up to approximately 5 years (Cycle length=21 days) | — |
| Substudy 2: Percentage of Participants With Positive ADA for DS-1103a Dosed in Combination With DS-3939a | Up to approximately 5 years | — |
Contacts
CONTACTDaiichi Sankyo Contact for Clinical Trial Information
Outcome results
None listed