First -in-Human Study of DS-3939a in Subjects with Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Mar 2025 → ongoing

Decision date (initial)

2024-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc.

External identifiers

EU CT number

2023-507937-14-00

ClinicalTrials.gov

NCT05875168

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Others, Pharmacokinetic, Efficacy, Pharmacogenomic, Pharmacodynamic

Part 1:
• Evaluate the safety and tolerability of DS-3939a
Part 2:
• Evaluate the safety and tolerability of DS-3939a at Recommended Dose for Expansion (RDE(s))
• Evaluate Objective Response Rate (ORR) of subjects treated with DS-3939a

Secondary objectives 4

1. Investigate the efficacy of DS-3939a.
2. Evaluate TA-MUC1expression in tumor tissue and its correlationwith DS-3939a efficacy.
3. Assess Pharmacokinetics (PK) properties of total conjugated payload, total anti-TA-MUC1 antibody, and free payload.
4. Assess the immunogenicity of DS-3939a.

Conditions and MedDRA coding

Metastatic Solid Tumor

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Sign and date the main Informed Consent Form (ICF).
2. Has a left ventricular ejection fraction ≥50% by either an echocardiogram or multigated acquisition within 28 days of enrollment.
3. Has adequate organ function.
4. Measurable disease based on RECIST V1.1.
5. Eastern Cooperative Oncology Group performance status score of 0 or 1.
6. Additional inclusion criteria for Part 1: Has a histologically or cytologically documented locally advanced, metastatic, or unresectable solid malignat tumors.
7. 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.
8. Additional inclusion criteria for Part 2: Is able to provide either of the following baseline tumor samples: a. Fresh tumor biopsy samples meeting either of the following requirements that were obtained during the Screening Period, or o Fresh core needle biopsy sample o Biopsy samples obtained with forceps or cryobiopsy, such as bronchoscopic or transbronchial lung biopsy b. FFPE tumor tissue samples obtained by biopsy or surgery performed within 6 months before signing the 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 9

1. Has had prior treatment targeting mucin 1 (MUC1) or TA-MUC1.
2. Has spinal cord compression or clinically active CNS metastases.
3. 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.
4. 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.
5. Has active or uncontrolled human immunodeficiency virus (HIV) infection.
6. Has active or uncontrolled hepatitis B virus or hepatitis C virus infection.
7. Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
8. Has an active, known, or suspected autoimmune disease.
9. Current participation in other therapeutic investigational procedures, except for participation in Long Term Follow-Up without any investigational treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Dose-limiting Toxicities (DLTs) [Part 1 only], Treatmentemergent Adverse Events (TEAEs), Laboratory findings, electrocardiogram (ECG), vital signs, echocardiogram or multigated acquisition (ECHO/MUGA) findings, physical examination results
2. Objective Response Rate (ORR) [Part 2 only]

Secondary endpoints 9

1. Objective Response Rate (ORR) [Part 1 only]
2. Disease Control Rate (DCR)
3. Duration of Response (DoR)
4. Time to Response (TTR)
5. Progression Free Survival (PFS)
6. Overall Survival (OS)
7. TA-MUC1 Expression by Immunohistochemistry (IHC)
8. Plasma PK parameters (eg, AUClast, AUCtau, Cmax, Tmax, Ctrough, and t1/2) of total conjugated payload, total anti-TAMUC1 antibody, and free payload
9. Anti-drug Antibodies (ADAs) for DS-3939a (status and titers) at Baseline and on treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 11

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 2 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications