Clinical trial NCT06819735: Study of DT-7012 as a Single Agent and in Combination With an Immune Checkpoint Inhibitor in Participants With Advanced Solid Tumors
Official title: A Phase 1/2, Multicentre, Open-label Clinical Trial of DT-7012 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Participants With Selected Advanced Solid Tumors (DOMISOL, DOmain_therapeutics Monoclonal antIbody for SOLid Tumors)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Domain Therapeutics SA
Sponsor class: INDUSTRY
Collaborators: name: Domain Therapeutics SA
First posted: 2025-02-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 1/2, dose-escalation and cohort-expansion clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of DT-7012 (an anti-CCR8 monoclonal antibody) as a single agent and in combination with an immune checkpoint inhibitor in adult participants with selected advanced solid tumors.

Detailed description: This is a phase 1/2, first-in-human, multicenter, open-label clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of DT-7012, administered as monotherapy and in combination with an immune checkpoint inhibitor (ICI), in participants with selected recurrent advanced/metastatic solid tumors.

This study includes:

* a phase 1 Dose Escalation with two planned parts (part 1A which corresponds to a dose escalation of DT-7012 monotherapy and part 1B which will be initiated upon recommendation from the Safety Review Committee based on part 1A data and corresponds to a dose escalation of a combination of DT-7012 with an ICI)
* a subsequent phase 2 Cohort Expansion

The phase 1 aims at determining the recommended phase 2 dose (RP2D) and the maximum tolerated dose or maximum administered dose of DT-7012 as single agent and in combination with an ICI in participants with selected recurrent advanced/metastatic solid tumors.

The phase 2 will assess DT-7012 as monotherapy and/or in combination with an ICI in expansion cohorts of 2-3 specific tumor types.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed solid tumor, among selected cancer types, that is recurrent, locally advanced (i.e., not eligible for curative surgery or radiotherapy) or metastatic, has progressed after at least one line of systemic therapy and has no established curative option.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the local site investigator/radiologist.
* At least 1 tumour lesion accessible to biopsy per treating physician judgement.
* Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
* Adequate organ function.

Exclusion Criteria:

* Any unresolved AEs from previous anti-cancer therapies of grade ≥2, with the exception of alopecia.
* Prior severe immune-related AEs (irAEs) leading to immunotherapy treatment discontinuation.
* Major surgery or significant traumatic injury within 4 weeks prior to Cycle 1 Day 1 with unadequately recovered AEs and/or complications from the intervention prior to Cycle 1 Day 1.
* Prior radiotherapy within the 4 weeks prior to Cycle 1 Day 1 or limited field palliative radiotherapy within 2 weeks prior to Cycle 1 Day 1.
* Prior anti-CCR8 monoclonal antibody treatment received in an investigational trial

Primary outcomes:
measure: Proportion of participants with DLTs, TEAEs, AESIs, SAEs and AEs leading to treatment discontinuation
timeFrame: Cycle 1 (21 days)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: From the first dose of study drug until the date of disease progression/recurrence, assessed up to 12 months
measure: Serum concentrations of DT-7012
timeFrame: From the first dose of study drug until the date of end of treatment, assessed up to 12 months
Other outcomes:
Locations:
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology & Oncology Group
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Health Limited
state: Victoria
Study officials:
References: