Advanced Solid Tumor
Conditions
Keywords
First-in-Human, Advanced Solid Tumors
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.
Interventions
DRUGDS5361b
Dose Escalation Part: DS5361b will be administered at escalating doses to determine the RDE. Dose Expansion Part: DS5361b will be administered at RDE.
DRUGPembrolizumab
Dose Escalation Part: Pembrolizumab will be administered at a standard dose. Dose Expansion Part: Pembrolizumab will be administered at a standard dose.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Number of participants with Dose-Limiting Toxicities (DLTs) | Cycle 1: Day 1 up to Day 21 (each cycle is 21 days) | 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. |
| Part 1, 2, and 3: Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) | From Screening up to approximately 5 years | 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). |
| Part 3 Only: Objective Response Rate (ORR) Following the Administration of DS5361b at RDE(s) in Combination with Pembrolizumab | From first dose up to approximately 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 | ORR is defined as the proportion of participants with a BOR of confirmed CR or PR, as assessed by investigator per RECIST v1.1. |
| Maximum Plasma Concentration (Cmax) of DS5361b | Cycle 1: Day 1, Day 15 (each cycle is 21 days) | — |
| Trough Plasma Concentration (Ctrough) of DS5361b | Cycle 1: Day 15 (each cycle is 21 days) | — |
| Disease Control Rate (DCR) Following Administration of DS5361b Alone and in Combination with Pembrolizumab | From first dose up to approximately 5 years | DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease as assessed by investigator per RECIST v1.1. |
| Duration of Response (DoR) Following Administration of DS5361b Alone and in Combination with Pembrolizumab | From first dose up to approximately 5 years | DoR is defined as the time (in months) from date of initial response (CR or PR) to the earlier date of the first objective documentation of radiographic disease progression or death due to any cause. |
Countries
Japan, United States
Contacts
CONTACTContact for Trial Information
Outcome results
None listed