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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: DS-1471a

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo@dsi.com
• Study Contact Backup: Name: Japanese sites only: Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: +81-3-6225-1111(M-F 9-5 JST); Email: dsclinicaltrial@daiichisankyo.co.jp

Study Locations

• Japan
  • Chiba, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
    • Contact: See Central Contact
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
    • Contact: See Central Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Dose Escalation Cohort 1: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 1, Dose Escalation Cohort 2: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 1, Dose Escalation Cohort 3: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 1, Dose Escalation Cohort 4: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 1, Dose Escalation Cohort 5: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 1, Dose Escalation Cohort 6: DS-1471a; Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.	Drug: DS-1471a; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 1): DS-1471a; 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; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 2): DS-1471a; 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; Intravenous administration on Day 1 of each 28-day cycle
Experimental: Part 2, Dose Expansion (Tumor-specific Cohort 3): DS-1471a; 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; Intravenous administration on Day 1 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 29, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Estimated): October 10, 2023

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Solid Tumor; DS-1471a
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: DS1471-079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No