Clinical trial NCT05856981: Phase 1 Study Evaluating the Safety and PK of ADU-1805 in Advanced Solid Tumors
Official title: An Open-Label, Multicenter, Multi-arm Phase 1 Study Evaluating the Safety and Pharmacokinetics of ADU-1805 in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor, Adult
Metastatic Solid Tumor
Refractory Cancer
Keywords: Immunotherapy
Lead sponsor: Sairopa B.V.
Sponsor class: INDUSTRY
First posted: 2023-05-12
Enrollment: 90
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 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of dose limiting toxicity (DLT), treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters
timeFrame: First 21 days of treatment
Secondary outcomes:
measure: Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters
timeFrame: Through study completion, up to 2,5 years
measure: Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters
timeFrame: Through study completion, up to 2,5 years
measure: Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters
timeFrame: Through study completion, up to 2,5 years
measure: Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
measure: Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through end of treatment, up to 2 years
measure: Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through end of treatment, up to 2 years
measure: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
measure: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
measure: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
measure: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
measure: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab
timeFrame: Through study completion, up to 2,5 years
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: St. Louis
country: United States
facility: Washington University Medical Campus
state: Missouri
city: Huntersville
country: United States
facility: Carolina BioOncology Institute - Cancer Research Clinic
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer & Research Center
state: Ohio
city: FairFax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi (GHdC) - Hopital Notre Dame
city: Chișinău
country: Moldova, Republic of
facility: National Institute of Oncology
city: Madrid
country: Spain
facility: Hosp 12 de Octubre
city: Madrid
country: Spain
facility: Hospital General Universitario Gergorio Maranon
Study officials:
References: