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

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

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).

This study is designed to evaluate the safety, PK, PD and preliminary clinical activity of ADU-1805, an anti- SIRPα monoclonal antibody, as monotherapy and in combination with pembrolizumab (anti-PD-1 antibody). The study is divided into a dose escalation phase and a dose expansion phase.

The dose expansion phase investigates ADU-1805 plus pembrolizumab at the respective recommended phase 2 dose (RP2D) in four advanced solid tumors: advanced PD-(L)1-naïve MSS colorectal cancer (CRC), PD-1 relapsed/refractory patients with either advanced MSS endometrial cancer (EC), renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC) patients.

Inclusion Criteria:

• Male or female aged ≥18 years
• Signed and dated informed consent form
• Measurable disease according to RECIST (Safety Expansion only)
• ECOG Performance status of 0 or 1
• Adequate organ and marrow function
• Escalation Phase: 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
• Expansion Phase: histologically and/or cytologically confirmed diagnosis of advanced PD-(L)1-naïve MSS colorectal cancer (CRC), PD-1 relapsed/refractory patients with either advanced MSS endometrial cancer (EC), renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC) patients, and that have measurable disease according to RECIST

Exclusion Criteria:

• Escalation Phase: Patients that suffer from melanoma, brain tumors, glioblastoma, sarcoma and pancreatic ductal adenocarcinoma (PDAC)

• Expansion Phase:

  • > 3 lines of prior systemic treatments
  • MSS colorectal cancer (CRC): liver metastasis present

• 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