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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor, Adult
• Interventions: Drug: DT-9081 - dose escalation; Drug: DT-9081 - expansion

• Registration Number: NCT05582850
• Lead Sponsor: Domain Therapeutics SA

Brief Summary

This is a Phase 1, multicentre, open-label, dose-escalation study to determine a recommended phase 2 dose (RP2D) of DT-9081, followed by an expansion study of DT-9081 in participants with advanced, recurrent or metastatic solid tumours

Detailed Description

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 modified 3+3 design with up to 8 dose escalation cohorts at increasing levels. The dose-escalation part aims at determining the recommended phase 2 dose. The second part is an expansion 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.

Study Timeline

• Study First Submitted: 2022-10-10
• Study First Submitted QC: 2022-10-12
• Study First Posted: 2022-10-17
• Study Start: 2022-11-24
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-07
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DT-9081	DT-9081 - dose escalation	Capsule, 25 mg, 50 mg and 100 mg
DT-9081	DT-9081 - expansion	Capsule, 25 mg, 50 mg and 100 mg

Primary Outcome Measures

Name	Time	Method
Dose escalation: safety assessment	Cycle 1 (28 days)	Number of dose-limiting toxicities (DLTs).
Dose escalation and expansion: safety assessment	From the first dose of study drug up to 30 days after the last dose of study drug	Incidence and severity of treatment-emergent AEs (TEAEs) and treatment-related TEAEs.
Dose escalation: recommended phase 2 dose (RP2D)	Cycle 1 (28 days)	The RP2D of DT-9081 is determined using pharmacokinetics, pharmacodynamics and safety data of the dose escalation part of the study.

Secondary Outcome Measures

Name	Time	Method
Preliminary anti-tumour activity	From the first dose of study drug until the date of disease progression/recurrence, assessed up to 48 months	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).
Dose escalation: maximum tolerated dose (MTD)	Cycle 1 (28 days)	The MTD will be determined based on safety data.
Maximum plasma concentration (Cmax)	Day 28 for each dose	Maximum concentration that DT-9081 achieves in plasma

Trial Locations

Locations (4)

Institut Jules Bordet; 🇧🇪 Anderlecht, Belgium

Université Catholique de Louvain; 🇧🇪 Louvain, Belgium

Institut Curie; 🇫🇷 Paris, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France