Advanced Cancers (Solid Tumors)
Conditions
Keywords
AWT020, anti-PD1, Interleukine-2, Phase 1
Brief summary
This study is aimed at establishing the MTD and/or the RP2D for AWT020 monotherapy and to provide safety, tolerability, efficacy, PK, immunogenicity characteristics of AWT020.
Detailed description
This study will enroll participants who have undergone at least one systemic therapy and have progressive disease during or after most recent line of therapy, and for whom no further standard therapy (that is known to confer clinical benefit) is available, or who are intolerant of standard therapy. The study design consists of two parts: dose escalation (BOIN design) and dose optimization. Participants enrolled into this study will be assigned to one of 4 dose levels and will receive AWT020 via intravenous infusion at a regular interval. The treatment will be continued until disease progression, withdrawal from study or death. The primary objective is to investigate the safety of this agent. The secondary objective is to investigate the pharmacokinetics, pharmacodynamic, potential anti-tumor activity and immunogenicity of this agent.
Interventions
BIOLOGICALAWT020
Participants receiving AWT020 once every three weeks at designated dose levels
Sponsors
Anwita Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older; able to provide written informed consent and comply with study visits and procedures. * Pathologically confirmed, unresectable advanced solid tumor. * Disease progression after at least one systemic therapy, with no beneficial standard option available or tolerated. Disease-specific prior therapy requirements apply to urothelial and renal cell carcinoma cohorts. * At least one measurable lesion by RECIST version 1.1, ECOG performance status of 0 or 1, and life expectancy of at least 3 months. * Adequate bone marrow, renal, hepatic, coagulation, and cardiac function as defined in the protocol. * Meets protocol requirements for reproductive safety and tumor tissue availability.
Exclusion criteria
* Relevant hypersensitivity or intolerance to prior immunotherapy, interleukin-2 based therapy, monoclonal antibodies, or the study treatment; or prior immunotherapy discontinued because of an immune-related adverse event. * Untreated or unstable central nervous system metastases, leptomeningeal disease, or brainstem metastases. * Clinically significant autoimmune or skin disease requiring systemic treatment; Stevens-Johnson syndrome or toxic epidermal necrolysis; or current, suspected, or steroid-treated interstitial lung disease/pneumonitis. * Unresolved toxicity from prior therapy, or recent anticancer treatment, major surgery, live vaccine, or other restricted therapy within protocol-defined washout periods. * Clinically significant cardiac, thromboembolic, cerebrovascular, gastrointestinal, bleeding, or other uncontrolled medical condition. * Active or recent severe infection. * Prior allogeneic transplantation or adoptive cellular immunotherapy; concurrent investigational therapeutic trial; or pregnancy or breastfeeding. * Another malignancy within 5 years, except permitted low-risk or in situ cancers; or any condition that increases risk, prevents consent or compliance, or could interfere with study interpretation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) [Safety] | Throughout the study up to 30 months | Type, incidence, and severity of Adverse Events (AEs) |
| Serious Adverse Events (SAEs) [Safety] | Throughout the study up to 30 months | Type, incidence, and severity of Serious Adverse Events (SAEs) |
| Treatment-emergent Adverse Events (TEAEs) [Safety] | Throughout the study up to 30 months | Type, incidence, and severity of treatment-emergent adverse events (TEAEs) |
| Adverse Events of Special Interest (AESIs) [Safety] | Throughout the study up to 30 months | Type, incidence, and severity of adverse events of special interest (AESIs) |
| Dose-limiting Toxicities (DLTs) [Tolerability] | Throughout the study up to 30 months | Incidence of dose-limiting toxicity (DLT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) | Throughout the study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Time to Cmax (Tmax) | Throughout study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Area Under the Curve (AUC) | Throughout the study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Clearance (CL) | Throughout the study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Volume of Distribution (Vss) | Throughout the study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Half-life (t1/2) | Throughout the study up to 30 months | Blood samples will be collected to characterize the pharmacokinetics (PK) of AWT020 |
| Overall Response Rate (ORR) | Throughout study up to 30 months | Overall response rate (ORR) assessed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Disease Control Rate (DCR) | Throughout the study up to 30 months | Disease control rate (DCR) assessed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Progression-free Survival (PFS) | Throughout the study up to 30 months | Time to response and duration of response assessed by the Investigator according to RECIST version 1.1 |
| Immune-related ORR (iORR) | Throughout the study up to 30 months | Immune-related overall response rate (iORR) assessed by the Investigator according to immune RECIST (iRECIST) |
| Immune-related DCR (iDCR) | Throughout the study up to 30 months | Immune-related disease control rate (iDCR) assessed by the Investigator according to immune RECIST (iRECIST) |
| Immune-related PFS (iPFS) | Throughout the study up to 30 months | Immune-related progression-free survival (iPFS) assessed by the Investigator according to iRECIST |
| Immune-related TTR (iTTR) | Throughout the study up to 30 months | Immune-related time to response (iTTR) assessed by the Investigator according to iRECIST |
| Immune-related DOR (iDOR) | Throughout the study up to 30 months | Immune-related duration of response (iDOR) assessed by the Investigator according to iRECIST |
| Overall Survival | Throughout study up to 30 months | The time from first dose of study treatment to death from any cause |
| Immunogenicity of AWT020 | Throughout study up to 30 months | Incidence of anti-drug antibodies (ADAs) |
Countries
United States
Contacts
CONTACTLaksmi Wilson
PRINCIPAL_INVESTIGATORHarshad Amin, MD
Florida Clinical Trials Group
Outcome results
None listed