Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors
- Conditions
- Malignant Solid TumorAdvanced Solid Tumor
- Interventions
- Drug: Ifinatamab deruxtecan (I-DXd)
- Registration Number
- NCT04145622
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
This is a single group study of participants with advanced solid tumors who have not been cured by other treatments. It is the first time the drug will be used in humans, and will be in two parts.
The primary purpose of the parts are:
* Dose Escalation Part: To evaluate the safety and tolerability and to determine the maximum tolerated dose and the recommended dose for expansion of ifinatamab deruxtecan (I-DXd).
* Dose Expansion Part: To investigate the safety, tolerability and antitumor activity of I-DXd when administered as a single agent.
This study is expected to last approximately 5 years from the time the first participant is enrolled to the time the last participant is off the study.
The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless:
* they withdraw
* their disease gets worse
* they experience unacceptable side effects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by Investigator. Measurable lesions should not be from a previously irradiated site. If the lesion at a previously irradiated site is the only selectable target lesion, a radiological assessment showing significant progression of the irradiated lesion should be provided by the Investigator
- Has adequate cardiac, hematopoietic, renal and hepatic functions
- Has an adequate treatment washout period prior to start of study treatment
- Has a pathologically documented advanced/unresectable or metastatic head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, squamous and adenocarcinoma non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bladder cancer, sarcoma, endometrial cancer, melanoma, adenocarcinoma CRPC (primary neuroendocrine or histologically confirmed neuroendocrine differentiated prostate cancer is not allowed), breast cancer that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
For Expansion Cohort 4 2L ESCC participants only:
- Has disease progression a post platinum-based and an immune checkpoint inhibitor (ICI) treatment per global or local guidelines, with a maximum of one prior line of systemic therapy for unresectable advanced or metastatic ESCC.
- Has prior treatment with B7-H3 targeted agent, including I-DXd.
- Has had prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (e.g., trastuzumab deruxtecan) due to treatment-related toxicities.
- Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial GI tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
- Uncontrolled significant cardiovascular disease
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement, prior pneumonectomy, or requirement for supplemental oxygen
- Has an uncontrolled infection requiring systemic therapy.
- Has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the Investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose expansion Ifinatamab deruxtecan (I-DXd) Currently enrolling participants with advanced solid tumors who will receive I-DXd IV Q3W monotherapy at the recommended dose for expansion. Dose escalation Ifinatamab deruxtecan (I-DXd) Participants with advanced solid tumors who received I-DXd IV Q3W monotherapy during dose escalation phase. Enrollment to this phase is currently closed.
- Primary Outcome Measures
Name Time Method Evaluate the incidence of adverse events (AEs) Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Investigate the antitumor activity of ifinatamab deruxtecan (I-DXd) Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Evaluate the incidence of dose-limiting toxicities (DLTs) Day 1 to Day 21 in Cycle 1 in the dose escalation part
- Secondary Outcome Measures
Name Time Method Characterize the PK parameter Tmax Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Characterize the PK parameter Ctrough Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Characterize the PK parameter Cmax Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Characterize the PK parameter AUClast Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Characterize the PK parameter AUCtau Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) Assess the incidence of anti-drug antibodies (ADAs) Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Trial Locations
- Locations (24)
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Kindai University Hospital
🇯🇵Osaka-Sayama, Japan
Cedars-Sinai Medical Center- Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Sidney Kimmel Cancer Center - Thomas Jefferson
🇺🇸Philadelphia, Pennsylvania, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
MDACC (MD Anderson Cancer Center)
🇺🇸Houston, Texas, United States
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
Shizuoka Cancer Center Hospital and Research Institute
🇯🇵Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Showa University Hospital
🇯🇵Tokyo, Japan