This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
292
DS-8201a to be administered via intravenous (IV) dose. DS-8201a (DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.
DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e.
DS-8201a (DP) is to be administered via intravenous (IV) dose.
Sharp Memorial Hospital
San Diego, California, United States
Mayo Clinic
Jacksonville, Florida, United States
University of Louisville
Louisville, Kentucky, United States
Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Disease control rate (DCR) by independent central review was calculated as the proportion of participants demonstrating complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 6 weeks (±1week) from the first dosing date. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
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Dana Farber Cancer Institute
Boston, Massachusetts, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
UC Health Clinical Trials Office
Cincinnati, Ohio, United States
University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States
Aichi Cancer Center Hospital
Aichi, Japan
National Cancer Center Hospital East
Chiba, Japan
...and 4 more locations
Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Best overall response by independent central review was defined as the proportion of participants who achieved either complete response \[CR\], partial response \[PR\], stable disease (SD), progressive disease (PD), or were non-evaluable (NE) as per RECIST v1.1. CR was defined as a disappearance of all target lesions, PR at least a 30% decrease in the sum of diameters of target lesions, and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Duration of response (DoR) by independent central review was defined as the time between the date of the first complete response (CR) or partial response (PR) until the date of the first documentation of progressive disease (PD) or death due to any cause. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and PD as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time to response (TTR) by independent central review was defined as the time interval between the date of registration until the date at which the criteria were first met for complete response (CR) or partial response (PR). Only participants who achieved CR or PR were included in the TTR analysis. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Overall survival (OS) by independent central review was defined as the time interval from the date of enrollment to the date of death from any cause. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose
The serum PK parameters of DS-8201a and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method.
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods.
Time frame: Post first dose up to Day 147
Overview of Treatment-emergent Adverse Events
Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03.
Time frame: Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months