Advanced Solid Tumors
Conditions
Brief summary
This is a phase 1/2, dose-escalation, 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 Monotherapy Dose Escalation * a phase 1b Combination Dose Escalation (this part will be initiated upon recommendation from the Safety Review Committee based on Monotherapy Dose Escalation data and corresponds to a dose escalation of a combination of DT-7012 with an ICI) * a subsequent phase 2 Indication-Specific Efficacy part The phase 1 aims at determining the maximum tolerated dose or maximum administered dose of DT-7012 as single agent and in combination with an ICI, and the safety and tolerability 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 the efficacy of DT-7012 as monotherapy and/or in combination with an ICI in indication-specific cohorts.
Interventions
DRUGDT-7012
Intravenous infusion
DRUGImmune checkpoint inhibitor
Intravenous infusion
Sponsors
Domain Therapeutics Australia Pty Ltd
Domain Therapeutics SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with DLTs, TEAEs, TRAEs, AESIs, SAEs and AEs leading to treatment discontinuation | Cycle 1 (21 days) | Proportion of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | From the first dose of study drug until the date of disease progression/recurrence, assessed up to 12 months | The anti-tumor 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) as assessed by the investigator. |
| Serum concentrations of DT-7012 | From the first dose of study drug until the date of end of treatment, assessed up to 12 months | Serum concentrations of DT-7012 will be determined to evaluate the pharmacokinetics (PK) of DT-7012 |
Countries
Australia, France, United States
Contacts
CONTACTClinical Development
Outcome results
None listed