A Study of DS5361b in Participants With Advanced Solid Tumors

Daiichi Sankyo

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Pembrolizumab; Drug: DS5361b

Study type: Interventional

Funder types: Industry

Identifiers

NCT07182591

DS5361-061

Details and patient eligibility

About

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.

Enrollment: 192 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

192 participants in 3 patient groups

Part 1: Monotherapy (Dose Escalation)

Experimental group

Description:

Participants will receive DS5361b at escalating doses.

Treatment:

Drug: DS5361b

Part 2: Combination Therapy (Dose Escalation)

Experimental group

Description:

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

Treatment:

Drug: DS5361b

Drug: Pembrolizumab

Part 3: Combination Therapy (Dose Expansion)

Experimental group

Description:

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

Treatment:

Drug: DS5361b

Drug: Pembrolizumab