Clinical trial NCT04145622: Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors
Official title: Phase I/II, Two-Part, Multicenter First-in-Human Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Subjects With Advanced Solid Malignant Tumors (IDeate-PanTumor01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Malignant Solid Tumor
Keywords: Advanced Solid Tumor
Malignant Tumor
Ifinatamab deruxtecan (I-DXd)
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-10-30
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Evaluate the incidence of dose-limiting toxicities (DLTs)
timeFrame: Day 1 to Day 21 in Cycle 1 in the dose escalation part
measure: Evaluate the incidence of adverse events (AEs)
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Investigate the antitumor activity of ifinatamab deruxtecan (I-DXd)
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary outcomes:
measure: Characterize the PK parameter AUClast
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Characterize the PK parameter AUCtau
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Characterize the PK parameter Cmax
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Characterize the PK parameter Tmax
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Characterize the PK parameter Ctrough
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
measure: Assess the incidence of anti-drug antibodies (ADAs)
timeFrame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center- Samuel Oschin Comprehensive Cancer Institute
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center - Thomas Jefferson
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MDACC (MD Anderson Cancer Center)
state: Texas
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center Hospital and Research Institute
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Showa University Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: