A Study of DS5361b in Participants With Advanced Solid Tumors

NCT07182591 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DS5361-061
• Study Type: interventional
• Target: 192
• Locations: 2 countries
• Sites: 7

Brief Summary

This study aims to assess the safety, tolerability, and preliminary efficacy and to determine the MTD of DS5361b in monotherapy and combination with pembrolizumab in participants with advanced or metastatic solid tumors.

Conditions

Advanced Solid Tumor

Keywords

First-in-Human; Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Part 1 and 2: Number of participants with Dose-Limiting Toxicities (DLTs)

  A DLT is defined as any Treatment Emergent Adverse Event (TEAE) not attributable to disease or disease-related processes, environmental factors, unrelated trauma, etc, that occurs during the DLT evaluation period (Day 1 to the end of Cycle 1) and is Grade ≥3.

  Cycle 1: Day 1 up to Day 21 (each cycle is 21 days)

• Part 1, 2, and 3: Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)

  TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 30 days after the last dose date of trial intervention).

  From Screening up to approximately 5 years

• Part 3 Only: Objective Response Rate (ORR) Following the Administration of DS5361b at RDE(s) in Combination with Pembrolizumab

  ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by investigator per RECIST v1.1.

  From first dose up to approximately 5 years

Secondary Outcomes (7)

• Maximum Plasma Concentration (Cmax) of DS5361b

  Cycle 1: Day 1, Day 15 (each cycle is 21 days)

• Time to Reach Maximum Plasma Concentration (Tmax) of DS5361b

  Cycle 1: Day 1, Day 15 (each cycle is 21 days)

• Area Under the Plasma Concentration-time Curve up to the Last Quantifiable Time (AUClast) of DS5361b

  Cycle 1: Day 1 (each cycle is 21 days)

• Trough Plasma Concentration (Ctrough) of DS5361b

  Cycle 1: Day 15 (each cycle is 21 days)

• Part 1 and 2: Objective Response Rate (ORR) Following the Administration of DS5361b Alone and in Combination with Pembrolizumab

  From first dose up to approximately 5 years

Study Arms (3)

Part 1: Monotherapy (Dose Escalation)

EXPERIMENTAL

Participants will receive DS5361b at escalating doses.

Drug: DS5361b

Part 2: Combination Therapy (Dose Escalation)

EXPERIMENTAL

Participants will receive DS5361b at escalating doses in combination with Pembrolizumab.

Drug: DS5361b; Drug: Pembrolizumab

Part 3: Combination Therapy (Dose Expansion)

EXPERIMENTAL

Participants will receive DS5361b in combination with Pembrolizumab at the recommended dose for expansion (RDE).

Drug: DS5361b; Drug: Pembrolizumab

Interventions

DS5361b DRUG

Dose Escalation Part: DS5361b will be administered at escalating doses to determine the RDE. Dose Expansion Part: DS5361b will be administered at RDE.

Part 1: Monotherapy (Dose Escalation); Part 2: Combination Therapy (Dose Escalation); Part 3: Combination Therapy (Dose Expansion)

Pembrolizumab DRUG

Dose Escalation Part: Pembrolizumab will be administered at a standard dose. Dose Expansion Part: Pembrolizumab will be administered at a standard dose.

Also known as: Keytruda®

Part 2: Combination Therapy (Dose Escalation); Part 3: Combination Therapy (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old).
• Has histologically- or cytologically documented recurrent, metastatic, or unresectable solid tumors that are refractory to or intolerable with standard treatment or for which no standard treatment is available (For Part 1 and Part 2 only).
• Participants need to have documented TMB or MSI status using a validated or approved genomic test as per applicable regulations prior to Cycle 1 Day 1. In Part 1 and Part 2, participants need to have documented TMB-H and/or MSI-H status. In Part 3, participants need to have documented TMB-H status.
• Has measurable disease based on local CT/MRI imaging as assessment by the investigator using RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention.
• For HNSCC participants only: have documented results from local testing of HPV for oropharyngeal cancer. If HPV status has previously been tested using this procedure, no retesting is required.
• Dose Expansion (Part 3) Only:
• Has histologically or cytologically confirmed, Stage IV NSCLC without actionable gene alteration.
• No prior systemic therapy.
• Participants with PD-L1 TPS ≥1%.
• Has histologically or cytologically confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies.
• No prior systemic therapy administered in the recurrent or metastatic setting.
• Participants with PD-L1 CPS ≥1.

You may not qualify if:

• Has spinal cord compression or clinically active central nervous system metastases.
• Has a history of leptomeningeal carcinomatosis.
• Uncontrolled or significant cardiovascular disease.
• Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
• Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out.
• Clinically severe pulmonary compromise (ie, requiring any supplemental oxygen).
• Has any evidence of severe or uncontrolled systemic diseases.
• Has active or uncontrolled HBV infection. Hepatitis B SCR testing is required.
• Has active or uncontrolled HCV infection. Hepatitis C SCR testing is required.
• For the dose escalation phase (Part 1 and Part 2), has HIV infection. For the dose expansion part (Part 3), has active or uncontrolled HIV infection.
• Prior organ transplantation, including allogeneic stem cell transplantation.
• Has an active, known, or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the trial intervention.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (7)

Research Site

Sarasota, Florida, 34232, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Irving, Texas, 75039, United States

RECRUITING

Research Site

San Antonio, Texas, 78229, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

NOT YET RECRUITING

Research Site

Chiba, 277-8577, Japan

RECRUITING

Research Site

Kōtoku, 135-8550, Japan

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Central Study Contacts

Contact for Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 19, 2025
• Study Start: October 2, 2025
• Primary Completion (Estimated): March 18, 2030
• Study Completion (Estimated): December 3, 2030
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

JP (2); US (5)