Study of DT-7012 as a Single Agent and in Combination With an Immune Checkpoint Inhibitor in Participants With Advanced Solid Tumors

Phase 1

Recruiting

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Part 1A	DT-7012	Dose escalation of DT-7012 as a single agent
Part 1B	Immune checkpoint inhibitor	Dose escalation of DT-7012 in combination with an ICI
Phase 2	Immune checkpoint inhibitor	Evaluation of DT-7012 as a sinle agent and/or in combination with an immune checkpoint inhibitor in expansion cohorts of 2-3 specific tumour types.
Part 1B	DT-7012	Dose escalation of DT-7012 in combination with an ICI
Phase 2	DT-7012	Evaluation of DT-7012 as a sinle agent and/or in combination with an immune checkpoint inhibitor in expansion cohorts of 2-3 specific tumour types.

Primary Outcome Measures

Name	Time	Method
Proportion of participants with DLTs, TEAEs, 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), adverse events of special intereswt (AESIs), serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation

Secondary Outcome Measures

Name	Time	Method
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

Locations (2): Peninsula & South Eastern Haematology & Oncology Group
🇦🇺
Frankston, Victoria, Australia
Cabrini Health Limited
🇦🇺
Malvern, Victoria, Australia
Peninsula & South Eastern Haematology & Oncology Group
🇦🇺Frankston, Victoria, Australia