Overview
This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of XTX101 as monotherapy and XTX101 and atezolizumab combination therapy in patients with advanced solid tumors.
Description
This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of XTX101, a tumor-selective anti-CTLA-4 antibody, as monotherapy and XTX101 and atezolizumab combination therapy in patients with advanced solid tumors.
Part 1A will examine XTX101 monotherapy in an accelerated and standard 3+3 dose escalation design. Based on the results of Part 1A, patients with select advanced solid tumors will be enrolled in Part 1B, which will evaluate XTX101 monotherapy in relation to specific PD biomarkers.
Part 1C will examine XTX101 in combination with atezolizumab in a standard 3+3 dose escalation/dose de-escalation design.
Eligibility
Inclusion Criteria:
Disease Criteria -
- Part 1A and 1C: Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, or standard therapy is not curative or available;
- Part 1B:
- Any histologically or cytologically confirmed solid tumor malignancy for which anti-PD-1 or anti-PD-L1 treatment is approved and has progressed on or after prior anti-PD-1 or anti-PD-L1 therapy.
- Patients with metastatic castrate-resistant prostate cancer if they have progressed on at least 2 lines of systemic therapy
- Patients with extensive stage small cell lung cancer (SCLC) after at least 1 line of prior therapy
- Patients with microsatellite stable colorectal cancer after at least 2 lines of prior therapy
- ECOG performance status of 0 or 1
- Adequate organ function
- Part 1B and Part 1C only: measurable disease per iRECIST
Exclusion Criteria:
- Received prior treatment with anti-CTLA-4 therapy
- Received prior immune-checkpoint therapy and experienced Grade 3 or greater toxicity lasting greater than 6 weeks
- Received prior systemic anticancer therapy within 4 weeks prior to study treatment
- Received prior radiotherapy within 2 weeks prior to study treatment
- Has a diagnosis of immunodeficiency
- Has known malignancy (other than disease under study) that is progressing or has required active treatment within the past 3 years
- Has an active autoimmune disease that has required systemic treatment in past 2 years, including the use of disease modifying agents, corticosteroids or immunosuppressive drugs
- Has an active infection requiring systemic intravenous therapy within 4 weeks prior to study treatment, or oral therapy within 2 weeks prior to study treatment
- Has a history of severe hypersensitivity reaction (≥ Grade 3) to any study intervention and/or any of its excipients
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study