A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02)
- Conditions
- Recurrent or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT06330064
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
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; and cutaneous melanoma.
- Detailed Description
This study will evaluate the efficacy and safety of I-DXd in participants with recurrent or metastatic solid tumors previously treated with 1 or more systemic therapies for the selected tumor indication. The study will be divided into 2 parts: Stage 1 and Stage 2. Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed.
The HCC Safety Run-In (Phase 1) will assess the safety and tolerability of I-DXd in participants with HCC.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 520
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Endometrial Cancer Ifinatamab deruxtecan Participants with recurrent or metastatic endometrial cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 2: Head and Neck Squamous Cell Carcinoma Ifinatamab deruxtecan Participants with recurrent or metastatic head and neck squamous carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 3: Pancreatic Ductal Adenocarcinoma Ifinatamab deruxtecan Participants with recurrent or metastatic pancreatic ductal adenocarcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 4: Colorectal Cancer Ifinatamab deruxtecan Participants with recurrent or metastatic colorectal cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 5: Hepatocellular Carcinoma Ifinatamab deruxtecan Participants with recurrent or metastatic hepatocellular carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd at the determined dose. Cohort 6: Adenocarcinoma of esophagus, gastroesophageal junction, and stomach Ifinatamab deruxtecan Participants with recurrent or metastatic adenocarcinoma of esophagus, gastroesophageal junction, and stomach who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 8: Ovarian cancer Ifinatamab deruxtecan Participants with recurrent or metastatic non-squamous ovarian cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 9: Cervical cancer Ifinatamab deruxtecan Participants with recurrent or metastatic cervical cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 10: Biliary tract cancer Ifinatamab deruxtecan Participants with recurrent or metastatic biliary tract cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 11: Human epidermal growth factor 2 (HER2)-low breast cancer Ifinatamab deruxtecan Participants with recurrent or metastatic human epidermal growth factor 2 (HER2)-low breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 12: HER2 immunohistochemistry (IHC) 0 breast cancer Ifinatamab deruxtecan Participants with recurrent or metastatic HER2 immunohistochemistry (IHC) 0 breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 7: Urothelial carcinoma Ifinatamab deruxtecan Participants with recurrent or metastatic urothelial carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg. Cohort 13: Cutaneous melanoma Ifinatamab deruxtecan Participants with recurrent or metastatic cutaneous melanoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Treatment-emergent Adverse Events and Death in the HCC Cohort From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.
Number of Participants Reporting Dose-limiting Toxicities in the HCC Cohort Cycle 1 Day 1 to Cycle 1 Day 21 A dose-limiting toxicity (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.
Objective Response Rate (ORR) as Assessed by Investigator 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 57 months ORR is defined as the proportion 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Have Treatment-emergent ADA Baseline up to 57 months Anti-drug antibodies will be measured in the plasma using a validated assay.
Progression-free Survival (PFS) 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 57 months PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of objective progressive disease (PD) per RECIST v1.1 or death due to any cause. PFS will be determined by the Investigator.
Pharmacokinetic Parameter Half-life (t1/2) for I DXd, total anti-B7-H3 antibody, and DXd Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days) Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Duration of Response (DoR) From the time of the first dose of study drug until the date of documented disease progression (confirmed by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months DoR is defined as the time from the first documented confirmed response (CR or PR) to the date of progression or death due to any cause as assessed by Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target and non-target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Disease Control Rate (DCR) 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 57 months DCR is defined as the proportion 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 was defined as a disappearance of all target and non-target lesions, PR was defined 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.
Pharmacokinetic Parameter Minimum Concentration (Ctrough) for I DXd, total anti-B7-H3 antibody, and DXd Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days) Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (TMax) for I DXd, total anti-B7-H3 antibody, and DXd Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days) Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. 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.
Pharmacokinetic Parameter Maximum Concentration (CMax) for I DXd, total anti-B7-H3 antibody, and DXd Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days) Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Pharmacokinetic Parameter Area Under the Curve (AUC) for I DXd, total anti-B7-H3 antibody, and DXd Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days) Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.
Overall Survival (OS) From the date of the first dose of drug up to the date of death due to any cause, up to approximately 57 months 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.
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Baseline up to 57 months Anti-drug antibodies will be measured in the plasma using a validated assay.
Trial Locations
- Locations (113)
Los Angeles Cancer Network
🇺🇸Los Angeles, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Pih Health Hematology Medical Oncology
🇺🇸Whittier, California, United States
Orchard Healthcare Research Inc.
🇺🇸Skokie, Illinois, United States
M Health Fairview University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
NYU Langone Health
🇺🇸New York, New York, United States
Icahn School of Medicine At Mount Sinai Prime
🇺🇸New York, New York, United States
Clinical Research Alliance
🇺🇸Westbury, New York, United States
Tn Gynecologic Oncology Group, Llc
🇺🇸Chattanooga, Tennessee, United States
The West Clinic
🇺🇸Germantown, Tennessee, United States
Scroll for more (103 remaining)Los Angeles Cancer Network🇺🇸Los Angeles, California, United StatesPrincipal InvestigatorContact