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

Solid Tumor, Adult Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05856981
• Other study ID #: SRP-22C102
• Status: Recruiting
• Phase: Phase 1
• Start date: April 3, 2023
• Est. completion date: December 2025

Study information

• Verified date: May 2023
• Source: Sairopa B.V.
• Contact: Sairopa Clinical Team
• Phone: 0031 85 90 26 939
• Email: clinical[@]sairopa.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-SIRPa 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

Related Conditions & MeSH terms

• Metastatic Solid Tumor
• Neoplasms
• Refractory Cancer
• Solid Tumor, Adult

Intervention

Drug:
• ADU-1805
anti-SIRPa monoclonal antibody
• Pembrolizumab
Keytruda

Locations

Country	Name	City	State
Moldova, Republic of	National Institute of Oncology	Chi?inau
United States	Gabrail Cancer & Research Center	Canton	Ohio
United States	Carolina BioOncology Institute - Cancer Research Clinic	Huntersville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sairopa B.V.

Countries where clinical trial is conducted

United States,  Moldova, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	Incidence of anti-ADU-antibodies	Through study completion, up to 2,5 years
Secondary	Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	DNA sequencing of SIRPa alleles	Through end of treatment, up to 2 years
Secondary	Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	Target engagement by ADU-1805	Through end of treatment, up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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