First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors

Official title

Phase 1/2, Open-label, Multicenter, First-in-Human Study of DS-3939a in Subjects With Advanced Solid Tumors

Overview

This study will evaluate the safety, tolerability, and efficacy of DS-3939a in participants with advanced solid tumors.

Detailed description

DS-3939a is an antibody drug conjugate (ADC) being developed for the treatment of malignant tumors. This is a first-in-human, dose-escalating clinical study divided into 2 parts: the Dose Escalation Part (Part 1) and the Dose Expansion Part (Part 2).

Interventions

• Drug DS-3939a
  One IV infusion Q3W on Day 1 of each 21-day cycle

Primary outcome measures

• Number of Participants with Dose-limiting Toxicities Following Treatment With DS-3939a [Time frame: Approximately 3 months after first dosing]
• Overall Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 2) [Time frame: Up to approximately 31 months]
• PSA50 Response Rate Following Treatment with DS-3939a (Part 2; CRPC only) [Time frame: Up to approximately 31 months]

Secondary outcome measures (12)

• Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 1) [Time frame: Up to approximately 31 months]
• Disease Control Rate Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• Duration of Response Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• Time to Response Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• Progression Free Survival Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• Overall Survival Following Treatment With DS-3939a [Time frame: Up to approximately 31 months]
• TA-MUC1 Expression by Immunohistochemistry Following Treatment With DS-3939a [Time frame: At Cycle 1 Day 1]
• Area Under the Plasma Concentration Curve (AUC) Following Treatment With DS-3939a [Time frame: Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)]
• Maximum Plasma Concentration (Cmax) Following Treatment With DS-3939a [Time frame: Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)]
• Time to Maximum Plasma Concentration (Tmax) Following Treatment With DS-3939a [Time frame: Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)]
• Minimum Observed Concentration (Ctrough) Following Treatment With DS-3939a [Time frame: Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)]
• Terminal Half-Life (T1/2) Following Treatment With DS-3939a [Time frame: Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)]

Eligibility criteria

Inclusion criteria

• Sign and date the main Informed Consent Form (ICF).
• Has a left ventricular ejection fraction ≥50% by either an echocardiogram or multigated acquisition within 28 days of enrollment.
• Has adequate organ function.
• Measurable disease based on RECIST V1.1.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.

Additional inclusion criteria for Part 1

• Has a histologically or cytologically documented locally advanced, metastatic, or unresectable solid malignant tumors.

Additional inclusion criteria for Part 2

• Has a histologically or cytologically documented locally advanced, metastatic, or unresectable cancer meeting the protocol criteria
• Is able to provide either of the following baseline tumor samples:

• Fresh tumor biopsy samples meeting either of the following requirements that were obtained during the Main Screening or Tissue Screening Period, or

• Fresh core needle biopsy sample
• Fresh biopsy samples obtained with forceps or cryobiopsy, such as bronchoscopic or transbronchial lung biopsy, or other procedures as long as the sample amount is equivalent to core needle biopsy and processing after sample collection follows the procedure described in the Study Laboratory Manual.
• FFPE tumor tissue samples obtained by biopsy or surgery performed within 6 months before signing the main ICF. If samples were obtained prior to the start of the most recent anticancer therapy, the Sponsor Medical Monitor should be consulted regarding the adequacy of the sample.

Exclusion criteria

• Has had prior treatment targeting mucin 1 (MUC1) or TA-MUC1.
• Has spinal cord compression or clinically active central nervous system metastases.
• Has multiple primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.
• Has any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids.
• Has active or uncontrolled human immunodeficiency virus (HIV) infection.
• Has evidence of active or uncontrolled hepatitis B virus or hepatitis C virus infection.
• Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
• Has an active (ie, symptomatic and/or on-treatment), known, or suspected autoimmune disease.
• Current participation in other therapeutic investigational procedures, except for participation in Long Term Follow-Up without any investigational treatment.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Florida Cancer Specialists — Sarasota
• Oregon Health & Science University — Portland
• Rhode Island Hospital — Providence
• University of Texas M.D. Anderson Cancer Center — Houston
• Huntsman Cancer Institute, University of Utah — Salt Lake City
• The Medical College of Wisconsin, INC — Milwaukee

Spain · 6 centers

• Hospital Universitari Vall D'Hebron — Barcelona
• Hospital Universitario Ramon Y Cajal — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Regional Universitario de Malaga — Málaga
• Next Madrid — Pozuelo de Alarcón
• Hospital Universitario Virgen Macarena — Seville

France · 5 centers

• Centre Léon Bérard — Lyon
• Assistance Publique- de Marseille — Marseille
• Chu Strasbourg — Strasbourg
• Institut Claudius Regaud — Toulouse
• Institut Gustave Roussy — Villejuif

Japan · 5 centers

• National Cancer Center Hospital — Chūōku
• Kansai Medical University Hospital — Hirakata-shi
• National Cancer Center Hospital East — Kashiwa
• Cancer Institute Hospital of Jfcr — Kōtoku
• Kindai University Hospital — Ōsaka-sayama

China · 4 centers

• Beijing Cancer Hospital — Beijing
• Shandong Cancer Hospital — Jinan
• The Second Peoples Hospital of Neijiang — Neijiang
• Shanghai East Hospital — Shanghai

South Korea · 4 centers

• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Canada · 2 centers

• McGill University Health Center — Montreal
• Princess Margaret Cancer Center — Toronto

Belgium · 1 center

• UZ Leuven — Leuven

Publications

• Takano K, Yukiura M, Takahashi K, Kitamura M, Okuno H, Shiose Y, Honda K, Oyama K, Yamada M, Obuchi W, Kumagai K, Sakurai K, Goto R, Zembutsu A, Kagari T, Abe Y, Agatsuma T. DS-3939a: A TA-MUC1-Directed Antibody-Drug Conjugate with Broad Antitumor Activity. Mol Cancer Ther. 2026 Jan 2;25(1):7-20. doi: 10.1158/1535-7163.MCT-24-0666. PMID 40635151

Identifiers

NCT: NCT05875168 · DS3939-077 · 2023-507937-14-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗