Study of Ifinatamab Deruxtecan (I-DXd) in Participants With Advanced Solid Malignant Tumors

Advanced Solid Tumor Clinical Trial

Official title:

Phase I/II, Two-Part, Multicenter First-in-Human Study of DS-7300a in Subjects With Advanced Solid Malignant Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04145622
• Other study ID #: DS7300-A-J101
• Secondary ID: 194992
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 3, 2019
• Est. completion date: March 1, 2027

Study information

• Verified date: January 2024
• Source: Daiichi Sankyo, Inc.
• Contact: (Japan sites) Daiichi Sankyo Contact for Clinical Trial Informat
• Phone: +81-3-6225-1111(M-F 9-5 JST)
• Email: dsclinicaltrial[@]daiichisankyo.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is in one single group 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: March 1, 2027
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Castrate-resistant prostate cancer (CRPC) participants with bone only disease may be eligible on a case-by- case basis after discussion with the Medical Monitor.
• 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.

Exclusion Criteria:

• Has prior treatment with B7-H3 targeted agent.
• Has prior treatment with an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan).
• 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Malignant Solid Tumor
• Neoplasms

Intervention

Drug:
• Ifinatamab deruxtecan (I-DXd)
A total anti-B7H3 antibody and MAAA-1181a

Locations

Country	Name	City	State
Japan	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	Cancer Institute Hospital of JFCR	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Japan	Showa University Hospital	Tokyo
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University	Columbus	Ohio
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	MDACC (MD Anderson Cancer Center)	Houston	Texas
United States	Cedars-Sinai Medical Center- Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Florida Cancer Specialists	Orlando	Florida
United States	Sidney Kimmel Cancer Center - Thomas Jefferson	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the incidence of dose-limiting toxicities (DLTs)		Day 1 to Day 21 in Cycle 1 in the dose escalation part
Primary	Evaluate the incidence of adverse events (AEs)		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Primary	Investigate the antitumor activity of ifinatamab deruxtecan (I-DXd)		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Characterize the PK parameter AUClast		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Characterize the PK parameter AUCtau		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Characterize the PK parameter Cmax		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Characterize the PK parameter Tmax		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Characterize the PK parameter Ctrough		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)
Secondary	Assess the incidence of anti-drug antibodies (ADAs)		Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)