Clinical trial NCT05875168: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: DS-3939a
anti-body drug conjugate
advanced/metastatic solid tumors
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2023-05-25
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

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 and documented radiographic disease progression during or after the most recent anticancer therapy.
* 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
  * Biopsy samples obtained with forceps or cryobiopsy, such as bronchoscopic or transbronchial lung biopsy (if 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 after the completion date of the most recent anticancer therapy regimen and within 6 months before signing the ICF

Exclusion Criteria:

* Has had prior treatment targeting mucin 1 (MUC1) or TA-MUC1.
* Has spinal cord compression or history of/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 a history of noninfectious interstitial lung disease (ILD)/pneumonitis (including suspected one), has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* 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, known, or suspected autoimmune disease.
* Current participation in other therapeutic investigational procedures, except for participation in Long Term Follow-Up without any investigational treatment.

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities Following Treatment With DS-3939a
timeFrame: Approximately 3 months after first dosing
measure: Overall Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 2)
timeFrame: Up to approximately 31 months
Secondary outcomes:
measure: Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 1)
timeFrame: Up to approximately 31 months
measure: Disease Control Rate Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: Duration of Response Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: Time to Response Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: Progression Free Survival Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: Overall Survival Following Treatment With DS-3939a
timeFrame: Up to approximately 31 months
measure: TA-MUC1 Expression by Immunohistochemistry Following Treatment With DS-3939a
timeFrame: At Cycle 1 Day 1
measure: Area Under the Plasma Concentration Curve (AUC) Following Treatment With DS-3939a
timeFrame: 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)
measure: Maximum Plasma Concentration (Cmax) Following Treatment With DS-3939a
timeFrame: 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)
measure: Time to Maximum Plasma Concentration (Tmax) Following Treatment With DS-3939a
timeFrame: 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)
measure: Minimum Observed Concentration (Ctrough) Following Treatment With DS-3939a
timeFrame: 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)
measure: Terminal Half-Life (T1/2) Following Treatment With DS-3939a
timeFrame: 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)
measure: Number of Participants With Treatment-emergent Anti-drug Antibodies Following Treatment With DS-3939a
timeFrame: Up to approximately 47 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin, INC
state: Wisconsin
city: Leuven
country: Belgium
facility: UZ Leuven
city: Montreal
country: Canada
facility: McGill University Health Center
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Lyon
country: France
facility: Centre Léon Bérard
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of Jfcr
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Pozuelo de Alarcón
country: Spain
facility: Next Madrid
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: