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)

Overview

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.

Interventions

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

Primary outcome measures

• Evaluate the incidence of dose-limiting toxicities (DLTs) [Time frame: Day 1 to Day 21 in Cycle 1 in the dose escalation part]
• Evaluate the incidence of adverse events (AEs) [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Investigate the antitumor activity of ifinatamab deruxtecan (I-DXd) [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]

Secondary outcome measures (6)

• Characterize the PK parameter AUClast [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Characterize the PK parameter AUCtau [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Characterize the PK parameter Cmax [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Characterize the PK parameter Tmax [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Characterize the PK parameter Ctrough [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]
• Assess the incidence of anti-drug antibodies (ADAs) [Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• Cedars-Sinai Medical Center- Samuel Oschin Comprehensive Cancer Institute — Los Angeles
• Sarah Cannon Research Institute at HealthONE — Denver
• Florida Cancer Specialists — Orlando
• Florida Cancer Specialists — Sarasota
• Dana Farber Cancer Institute — Boston
• Henry Ford Hospital — Detroit
• Washington University — St Louis
• John Theurer Cancer Center at Hackensack University Medical Center — Hackensack
• … and 7 more centers

Japan · 13 centers

• Aichi Cancer Center Hospital — Aichi
• National Cancer Center Hospital East — Chiba
• Hokkaido University Hospital — Hokkaido
• Kobe City Medical Center General Hospital — Hyōgo
• Kagawa University Hospital — Kagawa
• The University of Osaka Hospital — Osaka
• Kindai University Hospital — Ōsaka-sayama
• Saitama Cancer Center — Saitama
• … and 5 more centers

Publications

• Johnson ML, Patel MR, Falchook GS, Koyama T, Gutierrez M, Awad MM, Piha-Paul SA, Friedman CF, Satoh T, Okamoto N, Singh J, Yoshizuka N, Windish HP, Qian M, Tran BP, Doi T. Ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, in patients with advanced solid tumours (IDeate-PanTumor01): dose-escalation results from a phase 1/2 trial. Lancet Oncol. 2026 Apr;27(4):491-501. doi: 10.1016/S14 PMID 41926962

Identifiers

NCT: NCT04145622 · DS7300-A-J101 · 194992

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗