Phase 1 Study Evaluating the Safety and PK of ADU-1805 in Advanced Solid Tumors

Study Overview
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Brief Summary
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This first-in-human, open-label, multicenter, multi-arm dose-escalation study is designed to evaluate the safety, PK, and PD of ADU-1805, an anti- SIRPα monoclonal antibody, as monotherapy and in combination with pembrolizumab (anti-PD-1 antibody).

Detailed Description
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The study will start with the ADU-1805 monotherapy dose escalation arm following an i3+3 design until the RP2D is defined. The ADU-1805 plus pembrolizumab dose escalation arm, also following an i3+3 design, will start after clearance of the ADU-1805 monotherapy dose level achieving maximum target engagement (e.g. ≥ 90% target engagement) and will continue until the RP2D for the combination is defined.

Official Title
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An Open-Label, Multicenter, Multi-arm Phase 1 Study Evaluating the Safety and Pharmacokinetics of ADU-1805 in Adults With Advanced Solid Tumors

Conditions
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Solid Tumor, Adult, Metastatic Solid Tumor, Refractory Cancer

Intervention / Treatment
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* Drug: ADU-1805
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥18 years Signed and dated informed consent form Histologically and/or cytologically confirmed diagnosis of metastatic or unresectable solid tumors that are refractory to standard therapy or for which no standard therapy exists Measurable disease according to RECIST (Safety Expansion only) ECOG Performance status of 0 or 1 Adequate organ and marrow function Exclusion Criteria: Patients that suffer from melanoma, brain tumors, glioblastoma, sarcoma and pancreatic ductal adenocarcinoma (PDAC) Pregnancy or breast-feeding Prior treatment with or receipt of: biological agents, including monoclonal antibodies and immunotherapies, within 28 days prior to the first dose of ADU-1805 chemotherapy, targeted small molecule therapy, hormonal therapy or radiation therapy within 21 days prior to the first dose of ADU-1805 and within 42 days for nitrosoureas and mitomycin C. anti-SIRPα or anti-CD47-directed therapy systemic chronic steroid therapy or immunosuppressive therapy within 14 days prior to the first dose of ADU-1805 other investigational new drug or investigational device within 28 days prior to the first dose of ADU-1805 vaccine containing live virus within 28 prior to the first dose of ADU-1805 Active untreated brain metastases Active infection requiring systemic therapy Impaired cardiac function or clinically significant cardiac disease Current Grade >2 toxicity related to prior anti-cancer therapy History of drug-induced severe immune-related adverse reaction Prior severe hypersensitivity to other monoclonal antibodies or ADU-1805 excipients Major surgery within defined period Diagnosis or positive test of HIV, hepatitis B, hepatitis C, or active tuberculosis Allogenic tissue/solid organ transplant Any intercurrent illness that is life-threatening or of such clinical significance that it would interfere with the patient's safety or ability to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy dose escalation, IV, Q3W, multiple dose levels<br>ADU-1805 monotherapy dose escalation | Drug: ADU-1805<br>* anti-SIRPα monoclonal antibody<br>|
| Experimental: Combination dose escalation, IV, Q3W, multiple dose levels, pembrolizumab at fixed dose<br>ADU-1805 plus pembrolizumab dose escalation | Drug: ADU-1805<br>* anti-SIRPα monoclonal antibody<br>Drug: Pembrolizumab<br>* Keytruda<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dose limiting toxicity (DLT), treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters | Incidence of DLTs and incidence and severity of TEAEs, classified according to NCI-CTCAE v. 5.0 | First 21 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters | Maximum concentration (Cmax) | Through study completion, up to 2,5 years | 
| Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters | Time of maximum concentration (Tmax) | Through study completion, up to 2,5 years | 
| Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters | Area under the curve (AUC) | Through study completion, up to 2,5 years | 
| Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Incidence of anti-ADU-antibodies | Through study completion, up to 2,5 years | 
| Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | DNA sequencing of SIRPα alleles | Through end of treatment, up to 2 years | 
| Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Target engagement by ADU-1805 | Through end of treatment, up to 2 years | 
| Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Overall response per (i)RECIST. | Through study completion, up to 2,5 years | 
| Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Duration of response per (i)RECIST. | Through study completion, up to 2,5 years | 
| Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Disease control per (i)RECIST | Through study completion, up to 2,5 years | 
| Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Duration of disease control per (i)RECIST | Through study completion, up to 2,5 years | 
| Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Progression-free survival per (i)RECIST | Through study completion, up to 2,5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy