CRC, Colorectal Cancer, Endometrial Cancer, Metastatic Solid Tumor, NSCLC (Advanced Non-small Cell Lung Cancer), RCC, Clear Cell Adenocarcinoma, Refractory Cancer, Solid Tumor, Adult
Conditions
Keywords
Immunotherapy
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
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.
Interventions
DRUGADU-1805
anti-SIRPα monoclonal antibody
DRUGPembrolizumab
Keytruda
Sponsors
Sairopa B.V.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Escalation Phase: 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 |
| Expansion Phase: Evaluate the clinical response of ADU-1805 plus pembrolizumab administered as an intravenous (IV) infusion. | Through study completion, up to 2,5 years | Objective tumor response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expansion Phase: To confirm safety of ADU-1805 in combination with pembrolizumab as an IV infusion | Through study completion, up to 2,5 years | Incidence and severity of treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters. |
| Escalation and Expansion Phase: Immunogenicity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Through study completion, up to 2,5 years | Incidence of anti-ADU-antibodies |
| Escalation and Expansion Phase: 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 | Serum concentration-time profiles and PK parameters (including Cmax, AUC) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Escalation and Expansion Phase: Pharmacodynamics of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Through end of treatment, up to 2 years | Investigate the mechanism of action and pharmacodynamics (PD) of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab using tumor tissue and blood biomarkers (e.g. immune monitoring) |
| Escalation and Expansion Phase: Preliminary Clinical activity of ADU-1805 monotherapy and ADU-1805 plus pembrolizumab | Through study completion, up to 2,5 years | Overall and duration of response per (i)RECIST, PFS, (duration) of disease control, OS |
Countries
Belgium, Spain, United States
Contacts
Primary ContactSairopa Clinical Team
Outcome results
None listed