First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and efficacy of DS-3939a in participants with advanced solid tumors.

Detailed Description
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DS-3939a is an antibody drug conjugate (ADC) being developed for the treatment of malignant tumors. This is a first-in-human, dose-escalating clinical study divided into 2 parts: the Dose Escalation Part (Part 1) and the Dose Expansion Part (Part 2).

Official Title
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Phase 1/2, Open-label, Multicenter, First-in-Human Study of DS-3939a in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: DS-3939a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign and date the Informed Consent Form (ICF). Has a left ventricular ejection fraction ≥50% by either an echocardiogram or multigated acquisition within 28 days of enrollment. Has adequate organ function. Measurable disease based on RECIST V1.1. Eastern Cooperative Oncology Group performance status score of 0 or 1. Additional inclusion criteria for Part 1 Has a histologically or cytologically documented locally advanced, metastatic, or unresectable urothelial, non-small cell lung, breast, ovarian, or biliary tract cancers, or pancreatic ductal adenocarcinoma, regardless of any molecular subtypes. Additional inclusion criteria for Part 2 Has a histologically or cytologically documented locally advanced, metastatic, or unresectable cancer meeting the protocol criteria and documented radiographic disease progression during or after the most recent anticancer therapy. Is able to provide either of the following baseline tumor samples: Fresh core needle biopsy samples obtained during the Screening Period, or Alternative FFPE tumor tissue samples obtained by biopsy or surgery performed after the completion date of the most recent anticancer therapy regimen and within 6 months before signing the ICF Exclusion Criteria: Has had prior treatment targeting mucin 1 (MUC1) or TA-MUC1. Has spinal cord compression or history of/clinically active central nervous system metastases. Has multiple primary malignancies, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years. Has a history of noninfectious interstitial lung disease (ILD)/pneumonitis (including suspected one), has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. Has active human immunodeficiency virus (HIV) infection as determined by plasma HIV ribonucleic acid viral load and cluster of differentiation 4 count. Has evidence of active hepatitis B virus or hepatitis C virus infection. Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event. Has an active, known, or suspected autoimmune disease. Current participation in other therapeutic investigational procedures, except for participation in Long Term Follow-Up without any investigational treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation (Part 1)<br>Participants with locally advanced, metastatic, or unresectable tumors who will receive an intravenous (IV) infusion of DS-3939a. | Drug: DS-3939a<br>* One IV infusion Q3W on Day 1 of each 21-day cycle<br>|
| Experimental: Dose Expansion (Part 2)<br>Multiple expansion cohorts targeting various advanced solid tumors. | Drug: DS-3939a<br>* One IV infusion Q3W on Day 1 of each 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose-limiting Toxicities Following Treatment With DS-3939a |  | Approximately 3 months after first dosing | 
| Overall Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 2) |  | Up to approximately 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 1) |  | Up to approximately 31 months | 
| Disease Control Rate Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| Duration of Response Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| Time to Response Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| Progression Free Survival Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| Overall Survival Following Treatment With DS-3939a |  | Up to approximately 31 months | 
| TA-MUC1 Expression by Immunohistochemistry Following Treatment With DS-3939a |  | At Cycle 1 Day 1 | 
| Area Under the Plasma Concentration Curve (AUC) Following Treatment With DS-3939a |  | Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days) | 
| Maximum Plasma Concentration (Cmax) Following Treatment With DS-3939a |  | Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days) | 
| Time to Maximum Plasma Concentration (Tmax) Following Treatment With DS-3939a |  | Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days) | 
| Minimum Observed Concentration (Ctrough) Following Treatment With DS-3939a |  | Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days) | 
| Terminal Half-Life (T1/2) Following Treatment With DS-3939a |  | Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days) | 
| Number of Participants With Treatment-emergent Anti-drug Antibodies Following Treatment With DS-3939a |  | Up to approximately 47 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DS-3939a, anti-body drug conjugate, advanced/metastatic solid tumors