Overview
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.
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.
Eligibility
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.
