DS5361b alone and with pembrolizumab for adults with advanced solid tumors

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

This trial will test whether the new drug DS5361b, given alone or with pembrolizumab, is safe and shows signs of benefit in adults with advanced or metastatic solid tumors that have high tumor mutational burden or microsatellite instability.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Daiichi Sankyo (Industry-sponsored)
• Drugs / interventions: pembrolizumab
• Locations: 7 sites (Sarasota, Florida and 6 other locations)
• Trial ID: NCT07182591 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, phase 1 dose-escalation and expansion trial of DS5361b as monotherapy and in combination with the anti-PD-1 antibody pembrolizumab in adults with advanced or metastatic solid tumors. The trial will enroll biomarker-selected patients with documented TMB-H and/or MSI-H status and measurable disease, using RECIST v1.1 to monitor tumor responses. Primary objectives focus on safety, tolerability, dose-limiting toxicities, and determining the maximum tolerated dose; secondary objectives include preliminary anti-tumor activity and pharmacokinetics. Participants will undergo regular imaging and clinical assessments while receiving study treatment at designated research sites.

Who should consider this trial

Good fit: Adults with recurrent, metastatic, or unresectable solid tumors refractory to or without standard treatment options who have documented TMB-H and/or MSI-H, measurable disease, and adequate performance status are the intended participants.

Not a fit: Patients whose tumors are not TMB-H or MSI-H, who have poor performance status, or who cannot tolerate immunotherapy or investigational agents are less likely to benefit from this trial.

Why it matters

Potential benefit: If successful, this could offer a new treatment option for biomarker-selected patients with advanced solid tumors and potentially improve response rates over existing therapies.

How similar studies have performed: Pembrolizumab has demonstrated clinical benefit in MSI-H and TMB-H tumors in prior trials, but DS5361b is first-in-human and its safety and activity are currently untested.

Eligibility criteria

Key Inclusion Criteria:

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

1. 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).
2. 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).
3. 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.
4. Has measurable disease based on local CT/MRI imaging as assessment by the investigator using RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
6. Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention.
7. 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:
8. Has histologically or cytologically confirmed, Stage IV NSCLC without actionable gene alteration.

   * No prior systemic therapy.
   * Participants with PD-L1 TPS ≥1%.
9. 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.

Key Exclusion Criteria:

1. Has spinal cord compression or clinically active central nervous system metastases.
2. Has a history of leptomeningeal carcinomatosis.
3. Uncontrolled or significant cardiovascular disease.
4. Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
5. 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.
6. Clinically severe pulmonary compromise (ie, requiring any supplemental oxygen).
7. Has any evidence of severe or uncontrolled systemic diseases.
8. Has active or uncontrolled HBV infection. Hepatitis B SCR testing is required.
9. Has active or uncontrolled HCV infection. Hepatitis C SCR testing is required.
10. 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.
11. Prior organ transplantation, including allogeneic stem cell transplantation.
12. Has an active, known, or suspected autoimmune disease.
13. 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.

Where this trial is running

Sarasota, Florida and 6 other locations

• Research Site — Sarasota, Florida, United States (Recruiting)
• Research Site — Providence, Rhode Island, United States (Recruiting)
• Research Site — Irving, Texas, United States (Recruiting)
• Research Site — San Antonio, Texas, United States (Recruiting)
• Research Site — Fairfax, Virginia, United States (Not_yet_recruiting)
• Research Site — Chiba, Japan (Recruiting)
• Research Site — Kōtoku, Japan (Recruiting)

Study contacts

• Study coordinator: Contact for Trial Information

Conditions Advanced Solid Tumor; First-in-Human; Advanced Solid Tumors