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This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.

The main purpose of the study is to evaluate the safety and tolerability of the combination
of elranatamab and carfilzomib and dexamethasone or elranatamab and maplirpacept.

There are 2 parts to this study. Part 1 will evaluate the safety and tolerability of
elranatamab when given in combination with carfilzomib plus dexamethasone. Part 2 has 2 arms.
The first will evaluate the safety and tolerability of elranatamab when given in combination
with maplirpacept. The second will identify the optimal dose(s) of elranatamab plus
maplirpacept.

All study medicines are given over 4-week cycles. Everyone taking part in this study will
receive elranatamab as a shot under the skin. Participants in Part 1 will also receive weekly
carfilzomib as an IV infusion (given directly into a vein) and dexamethasone either by mouth
(as a pill) or by IV infusion. Participants in Part 2 will receive elranatamab in combination
with maplirpacept as an IV infusion (given directly into a vein)

The investigators will examine the experiences of people receiving the study medicines. This
will help determine if the study medicines are safe and can be used for multiple myeloma
treatment. Participants will take part in this study for about 2 years after the first dose.

The goal of this Open-Label Study is to evaluate the safety and tolerability of PRTH-101
alone or in combination with pembrolizumab in adults with advance or metastatic solid tumors.

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.