This is first in human study of DFF332, a small molecule that targets a protein called HIF2α.
By acting on HIF2α, DFF332 may be able to stop the growth of certain types of cancer. DFF332
will be tested at different doses as single agent and in combination with Everolimus (RAD001,
an mTOR inhibitor), and also in combination with Spartalizumab (PDR001, an anti-PD1) plus
Taminadenant (NIR178, an adenosine A2A receptor antagonist), in patients with advanced clear
cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.
This is a first in human (FIH), Phase I/Ib, open-label, multi-center study of DFF332 as a
single agent and in combination with Everolimus or Spartalizumab plus Taminadenant in
patients with advanced clear cell renal cell carcinoma and other malignancies with HIF
The study consists of two parts, dose escalation and dose expansion. The dose escalation part
of the study will initially evaluate DFF332 single agent. Dose escalation groups receiving
DFF332 in combination with Everolimus or DFF332 in combination with Spartalizumab plus
Taminadenant will open after at least two dose levels of single agent DFF332 have been
The dose expansion part of single agent will include two treatment arms: Arm1A will enroll
ccRCC patients (age 18 yo or above) and Arm1B will enroll patients with malignancies
harboring HIF stabilizing mutations (age 12 yo and above). These include the following:
Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)
Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)
Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary
paraganglioma and pheochromocytoma syndrome)
Malignancies with EPAS1/HIF2A mutations
Malignancies with ELOC/TCEB1 mutations
The expansion part of the combination therapies will enroll patients with ccRCC and include
Arm2A (DFF332 with Everolimus) and Arm3A (DFF332 with Spartalizumab plus Taminadenant).
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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