Clinical Trials Search at Vanderbilt-Ingram Cancer Center

This Phase 1, multicenter, open-label, dose escalation study is designed to assess the
safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical
activity of FHD-286 administered orally as monotherapy or combination therapy, in subjects
with advanced hematologic malignancies.

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and
expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in
combination with standard of care options for the treatment of rrDLBCL. This study will be
divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will
enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in
combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx
with respect to progression-free survival (PFS) per Lugano response criteria by blinded
independent review committee (BICR); and that ZV in combination with bendamustine rituximab
(BR) is superior to BR with respect to PFS per Lugano response criteria by BICR.

This phase I trial is to find out the best dose, possible benefits and/or side effects of nilotinib given together with trametinib and dabrafenib in treating patients with BRAF V600 mutant melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Nilotinib, trametinib, and dabrafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nilotinib together with trametinib and dabrafenib may lower the chance of cancer growing or spreading.

The PIK3CA gene is frequently mutated in breast cancer, leading to disease aggressiveness and
patient mortality. Alpelisib, a small molecule that inhibits the activity of the PIK3CA gene
product PI3K, has demonstrated clinical benefit in cancer patients with this gene mutation.
However, hyperglycemia, an on-target toxicity associated with alpelisib that leads to
hyperinsulinemia, limits the drug's clinical efficacy and induces high grade hyperglycemia in
patients with baseline metabolic dysfunction, insulin resistance and/or elevated HbA1c.
Restoring insulin sensitivity and reduction in circulating concentrations of insulin have
been reported to improve the activity of alpelisib.

Evexomostat (SDX-7320) is a polymer-conjugate of a novel small molecule methionine
aminopeptidase 2 (MetAP2) inhibitor that has demonstrated the ability to reduce
alpelisib-induced hyperglycemia in multiple animal experiments and has demonstrated
synergistic anti-tumor activity independent of changes in glucose or insulin. Evexomostat was
well tolerated in a Phase 1 safety study in late-stage cancer patients and showed
improvements in insulin resistance for patients that presented with baseline elevated
insulin. Overall, the most common treatment-emergent adverse events with evexomostat (TEAEs)
were fatigue (44%), decreased appetite (38%), constipation and nausea (each 28%), and
diarrhea (22%). All other TEAEs occurred at an incidence <20%.

The purpose of this study is to characterize the safety of the triplet drug combination
(alpelisib, fulvestrant plus evexomostat), to test whether evexomostat, when given in
combination with alpelisib and fulvestrant will reduce the number and severity of
hyperglycemic events and/or reduce the number of anti-diabetic medications needed to control
the hyperglycemia for patients deemed at risk for alpelisib-induced hyperglycemia (baseline
elevated HbA1c or well-controlled type 2 diabetes), and to assess preliminary anti-tumor
efficacy and changes in key biomarkers and quality of life in this patient population.