A Study of DS5361b in Participants With Advanced Solid Tumors

Official title

A Phase 1, Open-label, Multicenter, First-in-Human Trial of DS5361b in Participants With Advanced Solid Tumors

Overview

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.

Interventions

• Drug DS5361b
  Dose Escalation Part: DS5361b will be administered at escalating doses to determine the RDE. Dose Expansion Part: DS5361b will be administered at RDE.
• Drug Pembrolizumab
  Dose Escalation Part: Pembrolizumab will be administered at a standard dose. Dose Expansion Part: Pembrolizumab will be administered at a standard dose.

Primary outcome measures

• Part 1 and 2: Number of participants with Dose-Limiting Toxicities (DLTs) [Time frame: 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) [Time frame: 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 [Time frame: From first dose up to approximately 5 years]

Secondary outcome measures (7)

• Maximum Plasma Concentration (Cmax) of DS5361b [Time frame: Cycle 1: Day 1, Day 15 (each cycle is 21 days)]
• Time to Reach Maximum Plasma Concentration (Tmax) of DS5361b [Time frame: 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 [Time frame: Cycle 1: Day 1 (each cycle is 21 days)]
• Trough Plasma Concentration (Ctrough) of DS5361b [Time frame: 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 [Time frame: From first dose up to approximately 5 years]
• Disease Control Rate (DCR) Following Administration of DS5361b Alone and in Combination with Pembrolizumab [Time frame: From first dose up to approximately 5 years]
• Duration of Response (DoR) Following Administration of DS5361b Alone and in Combination with Pembrolizumab [Time frame: From first dose up to approximately 5 years]

Eligibility criteria

Inclusion criteria

The clinical site will screen for the full inclusion criteria per protocol.

• 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.

Exclusion criteria

• 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.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Research Site — Sarasota
• Research Site — Providence
• Research Site — Irving
• Research Site — San Antonio
• Research Site — Fairfax

Japan · 2 centers

• Research Site — Kashiwa
• Research Site — Kōtoku

Identifiers

NCT: NCT07182591 · DS5361-061

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗