This study will evaluate the safety and efficacy of DS-1103a combination therapy in participants with advanced solid tumors.
DS-1103a, a recombinant humanized IgG4 anti-SIRPα antibody designed to block the SIRPα-CD47 interaction, is being developed for the treatment of advanced cancers in combination with other anticancer therapies. This is the first-in-human, dose-escalation and dose-expansion clinical study designed to assess the safety and efficacy of DS-1103a combination therapy in participants with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
108
Florida Cancer Specialists
Sarasota, Florida, United States
RECRUITINGLifespan Cancer Institute
Providence, Rhode Island, United States
RECRUITINGNumber of Participants with Dose-limiting Toxicities (Dose Escalation)
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 21 (each cycle is 21 days)
Number of Participants with Dose-limiting Toxicities Following DS-1103a Combination Therapy (Dose Expansion; Cohort 2)
Time frame: From Cycle 1 Day 1 to Cycle 1 Day 21 (each cycle is 21 days)
Overall Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (Dose Escalation and Dose Expansion)
Time frame: Screening through long-term follow up, up to approximately 91 months
Objective Response Rate Assessed by Blinded Independent Central Review Following DS-1103a Combination Therapy (Dose Expansion)
Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors v1.1.
Time frame: Baseline (Dose Expansion) up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years 11 months
Objective Response Rate Assessed by Investigator (Dose Escalation and Dose Expansion)
Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Time frame: Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months
Disease Control Rate Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)
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University of Utah
Salt Lake City, Utah, United States
RECRUITINGNEXT Oncology
Fairfax, Virginia, United States
RECRUITINGPrincess Margaret Cancer Centre, University Health Network
Toronto, Canada
RECRUITINGOncopole - Institut Claudius Regaud
Toulouse, Haute Garonne, France
ACTIVE_NOT_RECRUITINGCentre Léon Bérard
Lyon, Rhone, France
ACTIVE_NOT_RECRUITINGCentre Léon Bérard
Lyon, France
RECRUITINGOncopole - Institut Claudius Regaud
Toulouse, France
RECRUITINGThe Cancer Institute Hospital Of JFCR
Tokyo, Japan
RECRUITING...and 1 more locations
Disease control rate is defined as the proportion of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) as assessed by the Investigator (Dose Escalation and Dose Expansion) and Blinded independent Central Review (BICR)(Dose Expansion) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Time frame: Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months
Clinical Benefit Rate Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)
Clinical benefit rate (CBR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting ≥183 days as assessed by the Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (BICR) (Dose Expansion) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Time frame: Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months
Duration of Response Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)
Duration of response (DoR) in a responding participant is defined as the time from the date of the first documentation of objective response (confirmed complete response \[CR\] or confirmed partial response \[PR\]) to the date of the first radiographic disease (as assessed by the Investigator \[Dose Escalation and Dose Expansion\] and Blinded Independent Central Review (BICR) \[Dose Expansion\]) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.
Time frame: Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months
Pharmacokinetic Parameter Area Under the Plasma Concentration Curve for DS-1103a (Dose Escalation and Dose Expansion)
Area under the plasma concentration-time curve up to the last quantifiable time (AUClast) and Area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.
Time frame: Dose Escalation: Cycles 1,2, and 4: Days 1,2,4,8,15; Cycle 3 Days 1,8,15; Cycle 6 and 8 Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4,6, and 8 Day 1 (each cycle is 21 days)
Pharmacokinetic Parameter Maximum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)
Maximum plasma concentration (Cmax) will be assessed using non-compartmental methods.
Time frame: Dose Escalation: Cycles 1,2, and 4: Days 1,2,4,8,15; Cycle 3 Days 1,8,15; Cycle 6 and 8 Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4,6, and 8 Day 1 (each cycle is 21 days)
Pharmacokinetic Parameter Time to Maximum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)
Time to maximum plasma concentration (Tmax) will be assessed using non-compartmental methods.
Time frame: Dose Escalation: Cycles 1,2, and 4: Days 1,2,4,8,15; Cycle 3 Days 1,8,15; Cycle 6 and 8 Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4,6, and 8 Day 1 (each cycle is 21 days)
Pharmacokinetic Parameter Minimum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)
Minimum plasma concentration (Cmin) will be assessed using non-compartmental methods.
Time frame: Dose Escalation: Cycles 1,2, and 4: Days 1,2,4,8,15; Cycle 3 Days 1,8,15; Cycle 6 and 8 Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4,6, and 8 Day 1 (each cycle is 21 days)
Number of Participants With Treatment-emergent Anti-drug Antibodies(ADAs) (Dose Escalation and Dose Expansion)
Time frame: Cycle 1 (D1, D15), Cycle 2 (D1, D15 [Dose Escalation only]), Cycles 3 and 4 (D1), thereafter every 2 cycles (D1), EOT, 40-day and 3-month (mth) follow-up (FU). ADA collection will occur as specified in protocol if pts are ADA positive at 3 mths.