This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) and in patients with lymphoma. TAK-243 is a drug that binds to and inhibits the ubiquitin-activating enzyme, an enzyme that is more active on cancer cells than healthy cells, inhibiting tumor cell proliferation and survival.
Patients with histologically documented advanced or metastatic solid tumors with relapsed or refractory disease who have received standard-of-care or approved therapies known to confer clinical benefit, or patients with aggressive lymphomas who have received ≥ 2 prior lines of lymphoma-directed therapy and who do not have remaining effective treatment options (including transplant). Additionally, patients with indolent lymphomas must meet criteria for treatment.
Patients must have measurable or evaluable disease
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patients who are receiving any other investigational agents
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
Life-threatening illness unrelated to cancer
Patients with uncontrolled coagulopathy or bleeding disorder
Parallel
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood
Computed Tomography
Procedure/SurgeryUndergo CT
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
UAE Inhibitor TAK-243
DrugGiven IV
Maximum tolerated dose (MTD)
The MTD for each arm will be based on the assessment of dose-limiting toxicities (DLTs) and will be defined as the dose level at which less than one-third of patients (\< 2/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (\>= 2/3 or \>= 2/6 patients) having DLT.
Recommended phase 2 dose
Incidence of DLTs
A DLT is defined as an adverse event that is felt to be related (possibly, probably, or definitely) to administration of study drugs, and meets pre-specified criteria. All toxicities will be reported for all patients who receive any amount of study drug on this study.
Pharmacodynamic (PD) variables
With 10 PD sample pairs, there is 90% power to detect a treatment effect equivalent to 1.8 standard deviations (associated with the inter-patient baseline variability of the PD marker) with the paired 2-sample t-test, at the 1-sided .01 significance level (to accommodate multiple endpoints while maintaining a reasonable over-all type 1 error bound), for a given PD variable of interest. PD variables may be log-transformed to achieve more nearly normal distributions.
Objective tumor response
For each of the two administration schedule arms, the objective tumor response rate will be estimated for the entire patient population in a descriptive fashion, including a 2-sided 90% confidence interval.
Progression-free survival
Overall survival
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