Overview
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
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.
Eligibility
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
