DT-9081 Study in Participants With Advanced, Recurrent or Metastatic Solid Tumours

Study Overview
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Brief Summary
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This is a Phase 1, multicentre, open-label, dose-escalation study to determine a recommended clinical dose (RCD) of DT-9081, followed by an expansion study of DT-9081 at RCD in participants with advanced, recurrent or metastatic solid tumours

Detailed Description
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This first-in-human Phase 1, multicentre, open label study is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of DT-9081 in adult patients with advanced, recurrent or metastatic solid tumours who failed standard of care therapies. This Phase 1 study consists of 2 parts. The first part is a dose-escalation using a 3+3 design with up to 6 dose escalation cohorts at increasing levels. The dose-escalation part aims at determining the recommended clinical dose (RCD). The second part is an expansion at the RCD to validate the dose/schedule of administration as well as to assess preliminary efficacy of DT-9081. Patients will be dosed orally once daily. The schedule might be adjusted in case of toxicities.

Official Title
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A Phase 1, Multicentre, Open-label, Dose-escalation Study to Determine a Recommended Clinical Dose (RCD) of DT 9081, Followed by an Expansion Study of DT-9081 at RCD in Participants With Advanced, Recurrent or Metastatic Solid Tumours

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: DT-9081 - dose escalation
* Drug: DT-9081 - expansion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a histologically or cytologically confirmed advanced solid tumour that is locally advanced (i.e., not eligible for curative surgery or radiotherapy), recurrent or metastatic, and who have failed or are ineligible for standard of care therapies. Participants must be ≥18 years of age. Participants must have measurable disease per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Participants must have adequate organ function. Exclusion Criteria: Participants using drugs interfering with the COX-2 pathways or prohibited drugs. Participants with unresolved AEs from previous anti-cancer therapies of Grade ≥ 2 with exception of alopecia. Participants with Grade ≤ 2 neuropathy may be eligible. Participants who underwent major surgery or significant traumatic injury within 4 weeks prior to Cycle 1 Day 1 who have not recovered adequately from any AEs and/or complications from the intervention prior to starting study drug. Participants who have received prior radiotherapy within the last 4 weeks before start of study drug treatment (limited field palliative radiotherapy within 2 weeks). Participants who have already received EP4R antagonist in an investigational trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DT-9081<br>Capsule, 25 mg, 50 mg and 100 mg | Drug: DT-9081 - dose escalation<br>* Patients will be dosed orally once daily. The schedule might be adjusted in case of toxicities.<br>* Other names: Phase 1 dose-escalation part;Drug: DT-9081 - expansion<br>* A homogeneous patient population will receive DT-9081 at the recommended clinical dose (RCD).<br>* Other names: Phase 1 expansion part;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation: recommended clinical dose (RCD) | The RCD of DT-9081 is determined using pharmacokinetics, pharmacodynamics and safety data of the dose escalation part of the study. | Cycle 1 (28 days) | 
| Dose escalation: safety assessment | Number of dose-limiting toxicities (DLTs). | Cycle 1 (28 days) | 
| Dose escalation and expansion: safety assessment | Incidence and severity of treatment-emergent AEs (TEAEs) and treatment-related TEAEs. | From the first dose of study drug up to 30 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation: maximum tolerated dose (MTD) | The MTD will be determined based on safety data. | Cycle 1 (28 days) | 
| Maximum plasma concentration (Cmax) | Maximum concentration that DT-9081 achieves in plasma | Day 28 for each dose | 
| Preliminary anti-tumour activity | The preliminary anti-tumour activity will be determined based on the assessment of, but not limited to, the objective response rate (ORR). ORR is defined as the percentage of participants with a complete response (CR) or a partial response (PR) at any time during the study according to RECIST v1.1 and immune RECIST (iRECIST). | From the first dose of study drug until the date of disease progression/recurrence, assessed up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced cancer, Immuno-oncology