Advanced Solid Tumor
Conditions
Keywords
Advanced Solid Tumor, DS-1471a
Brief summary
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
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.
Interventions
DRUGDS-1471a
Intravenous administration on Day 1 of each 28-day cycle
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 1 on computed tomography (CT) or magnetic resonance imaging (MRI) * Is willing and able to provide tumor tissue (newly obtained or archived) * 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 * A female participant of childbearing potential is eligible to participate if the following conditions are met: * Not pregnant as confirmed by highly sensitive pregnancy test within 7 days prior to study drug administration (Cycle 1 Day 1) * Agrees to adhere to a highly effective contraceptive method and agrees not to donate eggs or freeze/store eggs, during the intervention period, and for 7 months following the last dose of study drug * A male participant is eligible to participate if he agrees to the following during the intervention period and for 4 months following the last dose of study drug: * Avoid donating sperm * Adhere to either abstinence or use of a condom during intercourse with a nonparticipant of childbearing potential PLUS partner use of an additional contraceptive method * 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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Baseline up to 60 months | 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. |
| Progression-free Survival (PFS) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Escalation and Expansion) | Baseline up to 60 months | 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. |
| Overall Survival (OS) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Escalation and Expansion) | Baseline up to 60 months | 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. |
| Objective Response Rate (ORR) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Expansion) | Baseline up to 60 months | 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. |
| Disease Control Rate (DCR) of Participants With Advanced Solid Tumors Following Treatment With DS-1471a (Dose Expansion) | Baseline up to 60 months | 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). |
| Best Overall Response (BOR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Baseline up to 60 months | 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). |
| 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 | 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 | 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. |
| 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 | 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 | Anti-drug antibodies (ADA) incidence is defined as the proportion of participants having treatment-emergent ADAs. |
| 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 | — |
| Time to Response (TTR) As Assessed by the Investigator in Participants Following Treatment With DS-1471a (Dose Escalation and Expansion) | Baseline up to 60 months | 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. |
Countries
Japan, United States
Outcome results
None listed