This phase 1b/2 trial will investigate the safety of cabozantinib (Cabometyx) with or without atezolizumab (Tecentriq) in patients with advanced solid tumors.
The main outcomes will be maximum tolerated dose (MTD) and overall response rate (ORR).
Advanced cancers have limited treatment options. Surgery may not be possible. In many cases, chemotherapy or radiotherapy do not increase survival significantly. New drug targets are under investigation for advanced cancer. Tyrosine kinase inhibitors (TKIs) are one promising target. Cabozantinib (CBZ) is a TKI that slows tumor growth. It is currently approved for the treatment of advanced kidney and liver cancer. Immune checkpoint inhibitor (ICI) drugs are another promising new development in advanced cancer. Atezolizumab (ATZ) is a drug that blocks a protein called PD-L1. This enables the immune system to detect and kill tumor cells.
This trial will investigate the safety of CBZ in combination with ATZ in patients with advanced solid tumors. The main outcomes will be MTD and ORR.
Who are they looking for?
This trial will recruit 1732 participants with advanced solid tumors. This includes triple-negative breast cancer (TNBC). Patients must have an inoperable tumor. A tumor sample (biopsy) must be available for analysis. Adequate organ and bone marrow function are necessary. Sexually active subjects and their partners must use contraception to prevent pregnancy.
Patients cannot take part in the trial if they have been treated with CBZ or ICIs before. Patients with brain tumors are excluded from the trial. Patients with immune-related conditions, taking treatment with blood thinners and with another cancer diagnosis are excluded from the trial. Other exclusion criteria are recent vaccination or infection.
How will it work
There are two stages to the study. In the first stage, patients will be assigned to a combination dose of CBZ and ATZ. The dose of ATZ is standard (1200 mg every 3 weeks). The dose of CBZ will range between 20 and 60 mg daily. This will determine the maximum tolerated dose (MTD). After 6 months patients will enter the second phase. All patients will receive the MTD of CBZ and ATZ for up to 41 months.
The main outcomes will be MTD at 6 months and ORR at 31 months.