A Study of DS-1471a In Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This first-in-human (FIH) study will assess the safety, preliminary efficacy, pharmacokinetics (PK), and immunogenicity of DS-1471a in participants with advanced or metastatic solid tumors.

Detailed Description
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The objectives of this multinational, multicenter, open-label, 2-part, dose-escalation and dose-expansion, FIH study of participants with locally advanced or metastatic solid tumors are to evaluate the safety, maximum tolerated dose (MTD), recommended dose for expansion phase, preliminary efficacy, PK, and immunogenicity of DS-1471a.

Official Title
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A Phase 1, Multicenter, First-in-human Study of DS-1471a In Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: DS-1471a


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The clinical site will screen for the full inclusion criteria per protocol. Sign and date the informed consent form (ICF) Adults ≥18 years at the time the ICF is signed Has a histologically or cytologically documented, locally advanced, metastatic, or unresectable solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available Has at least 1 measurable lesion according to RECIST v1.1 Is willing and able to provide fresh tumor tissue biopsied at Baseline (mandatory) and on-treatment (mandatory if clinically allowed and not contraindicated) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 Life expectancy ≥3 months Has a left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to Cycle 1 Day 1 Required baseline local laboratory data (within 7 days prior to Cycle 1 Day 1) as prespecified in the protocol If the participant is a female of childbearing potential, she must have a negative serum pregnancy test within 7 days prior to study drug administration (Cycle 1 Day 1) and must be willing to use highly effective birth control upon enrollment, during the Treatment Period, and for 7 months following the last dose of study drug If male, the participant must be surgically sterile or willing to use highly effective birth control upon enrollment, during the Treatment Period, and for 4 months following the last dose of study drug Is willing and able to comply with scheduled visits, study drug administration plan, laboratory tests, other study procedures, and study restrictions Patients with liver cirrhosis and liver cancer may be eligible to participate if they meet additional protocol specified criteria Key Exclusion Criteria: The clinical site will screen for the full exclusion criteria per protocol. Has an inadequate treatment washout period prior to start of study treatment (Cycle 1 Day 1) as prespecified in the protocol Has history of or current presence of untreated central nervous system (CNS) metastases Has a history of leptomeningeal carcinomatosis Has a history of (non-infectious) interstitial lung disease (ILD) other than radiation pneumonitis, currently has ILD, or when suspected ILD cannot be ruled out by imaging at screening Has a history of severe pulmonary compromise or requirement of supplemental oxygen within 6 months before enrollment Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, arterial thromboembolic event, or pulmonary embolism Has uncontrolled or clinically significant cardiovascular disease Is requiring chronic steroid treatment (>10 mg daily prednisone equivalents) Has multiple primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial cancer in the gastrointestinal tract curatively resected by endoscopic surgery, or any other solid tumors curatively treated with no evidence of recurrent disease for ≥3 years Has unresolved toxicities from previous anticancer treatment Exposure to another investigational medical product within 4 weeks prior to Cycle 1 Day 1 or current participation in other therapeutic investigational procedures Has an active, known, or suspected autoimmune disease Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. Has an active hepatitis or uncontrolled hepatitis B or C infection, except for HCC participants with hepatitis B infection that is controlled by antiviral therapy Has human immunodeficiency virus (HIV) infection, with exceptions per protocol for participants in Dose Expansion Has received a live, attenuated vaccine (messenger RNA [mRNA] and replication-deficient adenoviral vaccines are not considered live, attenuated vaccines) within 30 days prior to first exposure to study drug (Cycle 1 Day 1) Female who is pregnant or breastfeeding or intends to become pregnant during the study Has psychological, social, familial, or geographical factors that would prevent regular follow-up Has prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1, Dose Escalation Cohort 1: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 1, Dose Escalation Cohort 2: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 1, Dose Escalation Cohort 3: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 1, Dose Escalation Cohort 4: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 1, Dose Escalation Cohort 5: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 1, Dose Escalation Cohort 6: DS-1471a<br>Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 1): DS-1471a<br>Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 2): DS-1471a<br>Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-day cycle<br>|
| Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 3): DS-1471a<br>Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation. | Drug: DS-1471a<br>* Intravenous administration on Day 1 of each 28-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-1471a (Dose Escalation) |  | Cycle 1: Baseline up to Day 28 (each cycle is 28 days) | 
| Number of Participants With Treatment-emergent Adverse Events Following Treatment With DS-1471a (Dose Escalation and Expansion) |  | Baseline up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Best overall response (BOR) is recorded from the start of study drug until documented progressive disease (PD) or start of any anticancer treatment, whichever occurs first. Confirmation of complete response (CR) or partial response (PR) is required. As per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, CR is defined as a disappearance of all target lesions, PR is defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). | Baseline up to 60 months | 
| Time to Response (TTR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Time to response (TTR) is defined as the time from the start of study drug to the date of the first documentation of response (CR or PR) as assessed by the investigator. As per RECIST v1.1, CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. | Baseline up to 60 months | 
| Duration of Response (DoR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Duration of response (DoR) is defined as the time from first documentation of CR or PR to the date of the first documentation of PD as assessed by the investigator or to the date of death due to any cause, whichever occurs first. As per RECIST v1.1, CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. | Baseline up to 60 months | 
| Progression-free Survival (PFS) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Escalation and Expansion) | Progression-free survival (PFS) is defined as the time from the start date of study drug to the date of the first documentation of objective PD as assessed by the investigator or to the date of death due to any cause, whichever occurs first. As per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. | Baseline up to 60 months | 
| Overall Survival (OS) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Escalation and Expansion) | Overall survival (OS) is defined as the time from the date of the start of study drug to the date of death due to any cause. | Baseline up to 60 months | 
| Objective Response Rate (ORR) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Expansion) | Confirmed objective response rate (ORR) is defined as the proportion of participants who have a confirmed BOR of CR or PR as assessed by the investigator. As per RECIST v1.1, CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. | Baseline up to 60 months | 
| Disease Control Rate (DCR) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Expansion) | Disease control rate (DCR) is defined as the proportion of participants who have a BOR of CR, PR, or SD as assessed by the investigator. As per RECIST v1.1, CR is defined as a disappearance of all target lesions, PR is defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). | Baseline up to 60 months | 
| Pharmacokinetic Analysis Maximum Plasma Concentration (Cmax) of DS-1471a |  | Cycle 1 (Days 1, 2, 4, 8, 15, and 22), Cycle 2 (Day 1), Cycle 3 (Days 1, 2, 4, 8, 15, and 22), Cycles 4, 6, and 8 (Day 1), each cycle is 28 days | 
| Pharmacokinetic Analysis Time to Reach Maximum Plasma Concentration (Tmax) of DS-1471a |  | Cycle 1 (Days 1, 2, 4, 8, 15, and 22), Cycle 2 (Day 1), Cycle 3 (Days 1, 2, 4, 8, 15, and 22), Cycles 4, 6, and 8 (Day 1), each cycle is 28 days | 
| Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve of DS-1471a | Area under the plasma concentration-time curve up to the last quantifiable time (AUClast), area under the plasma concentration-time curve from the time of dosing to 28 day (AUC28d), and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed. | Cycle 1 (Days 1, 2, 4, 8, 15, and 22), Cycle 2 (Day 1), Cycle 3 (Days 1, 2, 4, 8, 15, and 22), Cycles 4, 6, and 8 (Day 1), each cycle is 28 days | 
| Pharmacokinetic Analysis Trough Plasma Concentration (Ctrough) of DS-1471a |  | Cycle 1 (Days 1, 2, 4, 8, 15, and 22), Cycle 2 (Day 1), Cycle 3 (Days 1, 2, 4, 8, 15, and 22), Cycles 4, 6, and 8 (Day 1), each cycle is 28 days | 
| Percentage of Participants With Anti-Drug Antibodies Against DS-1471a | Anti-drug antibodies (ADA) incidence is defined as the proportion of participants having treatment-emergent ADAs. | Cycle 1 (Days 1 and 8), Cycle 2 and 3 (Day 1), and Cycle 4 and every 2 cycles thereafter (Day 1), each cycle is 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumor, DS-1471a