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

Phase 1

Recruiting

• Conditions: Refractory Cancer; Metastatic Solid Tumor; Solid Tumor, Adult
• Interventions: Drug: ADU-1805; Drug: Pembrolizumab

• Registration Number: NCT05856981
• Lead Sponsor: Sairopa B.V.

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.

Study Timeline

• Study First Submitted: 2023-01-04
• Study Start: 2023-04-03
• Status Verified: 2023-05
• Study First Submitted QC: 2023-05-03
• Study First Posted: 2023-05-12
• Last Update Submitted: 2023-05-26
• Last Update Posted: 2023-05-30
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy dose escalation, IV, Q3W, multiple dose levels	ADU-1805	ADU-1805 monotherapy dose escalation
Combination dose escalation, IV, Q3W, multiple dose levels, pembrolizumab at fixed dose	ADU-1805	ADU-1805 plus pembrolizumab dose escalation
Combination dose escalation, IV, Q3W, multiple dose levels, pembrolizumab at fixed dose	Pembrolizumab	ADU-1805 plus pembrolizumab dose escalation

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	Through study completion, up to 2,5 years	Progression-free survival per (i)RECIST
Pharmacokinetics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab, serum concentration-time profile and PK parameters	Through study completion, up to 2,5 years	Area under the curve (AUC)
Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	Through end of treatment, up to 2 years	Target engagement by ADU-1805
Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab	Through study completion, up to 2,5 years	Incidence of anti-ADU-antibodies

Trial Locations

Locations (3)

Gabrail Cancer & Research Center; 🇺🇸 Canton, Ohio, United States

National Institute of Oncology; 🇲🇩 Chișinău, Moldova, Republic of

Carolina BioOncology Institute - Cancer Research Clinic; 🇺🇸 Huntersville, North Carolina, United States