Study of DS-7300a in Participants With Advanced Solid Malignant Tumors

Study Overview
=================
Brief 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; DS-7300a). 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.

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

Conditions
-----------------
Advanced Solid Tumor, Malignant Solid Tumor

Intervention / Treatment
-----------------
* Drug: Ifinatamab deruxtecan (I-DXd)


Participation Criteria
=================
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. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>All participants enrolled in the dose escalation part | Drug: Ifinatamab deruxtecan (I-DXd)<br>* A total anti-B7H3 antibody and MAAA-1181a<br>* Other names: DS-7300a;|
| Experimental: Dose expansion<br>All participants enrolled in the dose expansion part | Drug: Ifinatamab deruxtecan (I-DXd)<br>* A total anti-B7H3 antibody and MAAA-1181a<br>* Other names: DS-7300a;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the incidence of dose-limiting toxicities (DLTs) |  | Day 1 to Day 21 in Cycle 1 in the dose escalation part | 
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Characterize the PK parameter Cmax |  | Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) | 
| 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) | 
| Assess the incidence of anti-drug antibodies (ADAs) |  | Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Solid Tumor, Malignant Tumor, Ifinatamab deruxtecan (I-DXd, DS-7300a)