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

A Phase 1, Multicentre, Open-label, Dose-escalation and Expansion Study to Determine a Recommended Phase 2 Dose (RP2D) of DT-9081 in Participants With Advanced Solid Tumours

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

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: DT-9081 - dose escalation; Drug: DT-9081 - expansion

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 Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Development, PhD; Phone Number: 0033390406150; Email: clinicaltrials@domaintherapeutics.com

Study Locations

• Belgium
  • Anderlecht, Belgium
    • Recruiting
    • Institut Jules Bordet
  • Louvain, Belgium
    • Recruiting
    • Université Catholique de Louvain
• France
  • Paris, France
    • Recruiting
    • Institut Curie
  • Toulouse, France
    • Recruiting
    • Institut Claudius Regaud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DT-9081; Capsule, 25 mg, 50 mg and 100 mg	Drug: DT-9081 - dose escalation; Patients will be dosed orally once daily. The schedule might be adjusted in case of toxicities.; Other Names: Phase 1 dose-escalation part; Drug: DT-9081 - expansion; A homogeneous patient population will receive DT-9081 at up to 3 dose levels.; Other Names: Phase 1 expansion part

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Dose escalation: recommended phase 2 dose (RP2D)	The RP2D of DT-9081 is determined using pharmacokinetics, pharmacodynamics and safety data of the dose escalation part of the study.	Cycle 1 (28 days)

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

Collaborators and Investigators

• Sponsor: Domain Therapeutics SA

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Advanced cancer; Immuno-oncology
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: DT-9081-CLI-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No