This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD) in the following tumor types: endometrial cancer (EC); head and neck squamous cell carcinoma (HNSCC); pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC); hepatocellular carcinoma (HCC); adenocarcinoma of esophagus, gastroesophageal junction, and stomach (Ad-Eso/GEJ/gastric); urothelial carcinoma (UC); ovarian cancer (OVC); cervical cancer (CC); biliary tract cancer (BTC); human epidermal growth factor 2 (HER2)-low breast cancer (BC); HER2 immunohistochemistry (IHC) 0 BC; cutaneous melanoma; and neuroendocrine carcinoma (NEC).
This study will evaluate the efficacy and safety of I-DXd in participants with recurrent or metastatic solid tumors. The study will be divided into 3 parts: Stage 1, Stage 2 and an optional Stage 3. Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed. The EC cohort may proceed to an optional Stage 3 expansion based on the totality of available data. The HCC Safety Run-In (Phase 1) will assess the safety and tolerability of I-DXd in participants with HCC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
680
Intravenous administration
Valkyrie Clinical Trials
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGLos Angeles Cancer Network
Los Angeles, California, United States
RECRUITINGPih Health Hematology Medical Oncology
Whittier, California, United States
RECRUITINGOrchard Healthcare Research Inc
Skokie, Illinois, United States
Objective Response Rate (ORR) as Assessed by Investigator
ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first (up to approximately 60 months)
Number of Participants Reporting Dose-limiting Toxicities (DLTs) in the HCC Cohort
A DLT is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT evaluation period (from C1D1 to the end of Cycle 1 in Safety Run-in) and is Grade 3 or above, according to NCI-CTCAE version 5.0, with the exceptions as noted in the protocol.
Time frame: Cycle 1 Day 1 to Cycle 1 Day 21
Number of Participants Reporting TEAEs and Death in the HCC Cohort
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs with start or worsening after the first dose date of I-DXd and up to 40 (+7) days after the last dose date of study drug.
Time frame: From date of signing the informed consent form up to 47 days after the last dose of study drug, up to approximately 60 months
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs with start or worsening after the first dose date of I-DXd and up to 40 (+7) days after the last dose date of study drug. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.
Time frame: From date of signing the informed consent form up to 47 days after the last dose of study drug, up to approximately 60 months
Duration of Response (DoR)
DoR is defined as the time from the date of first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first, as assessed by the Investigator per RECIST v1.1, respectively. CR is defined as a disappearance of all target and non-target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months
Progression-free Survival (PFS)
PFS is defined as the time interval from the date of the first dose of study drug to the date of disease progression as assessed by the investigator per RECIST v1.1 or death from any cause.
Time frame: From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) as assessed by the Investigator per RECIST v1.1, respectively. CR is defined as a disappearance of all target and non-target lesions, PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From the time of the first dose of study drug until the date of documented disease progression (by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months
Overall Survival (OS)
OS is defined as the time interval from the date of the first dose of study drug to the date of death from any cause.
Time frame: From the date of the first dose of drug up to the date of death due to any cause, up to approximately 60 months
Pharmacokinetic Parameter Maximum Concentration (CMax) for I DXd, total anti-B7-H3 antibody, and DXd
Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Time frame: Cycles1 & 3 Day1:pre-dose,end of infusion(EOI),post-dose at 3 hours(hr),6 hr;24 hr,168 hr;336 hr;504 hr; Cycles 2, 4, and 5 Day 1:pre-dose and EOI;Cycle 7 and every 2 cycles thereafter up to end of study(EOS)(60 months):pre-dose(every cycle is 21 days)]
Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (TMax) for I DXd, total anti-B7-H3 antibody, and DXd
Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Time frame: Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)]
Pharmacokinetic Parameter Half-life (t1/2) for I DXd, total anti-B7-H3 antibody, and DXd
Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Time frame: Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)]
Pharmacokinetic Parameter Minimum Concentration (Ctrough) for I DXd, total anti-B7-H3 antibody, and DXd
Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Time frame: Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)]
Pharmacokinetic Parameter Area Under the Curve (AUC) for I DXd, total anti-B7-H3 antibody, and DXd
Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Time frame: Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)]
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Anti-drug antibodies will be measured in plasma using a validated assay.
Time frame: Baseline up to 60 months
Percentage of Participants Who Have Treatment-emergent ADA
Anti-drug antibodies will be measured in plasma using a validated assay.
Time frame: Baseline up to 60 months
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M Health Fairview University of Minnesota Medical Center
Minneapolis, Minnesota, United States
RECRUITINGNYU Langone Health
New York, New York, United States
RECRUITINGIcahn School of Medicine At Mount Sinai Prime
New York, New York, United States
RECRUITINGClinical Research Alliance, Inc
Westbury, New York, United States
RECRUITINGWhite Plains Hospital
White Plains, New York, United States
RECRUITINGErlanger Health, Inc
Chattanooga, Tennessee, United States
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