An Open-Label Phase 2 Trial of Nanatinostat Plus Valganciclovir in Patients With EBV+ Relapsed/Refractory Lymphomas

Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.

Time frame: Up to approximately 2 years

Population: Intent-to-Treat Analysis Set, defined as all patients who were enrolled into the trial regardless of whether or not they received study treatment.~The study was not designed to make formal statistical comparisons of ORRs between cohorts.

Interval of time from date of first observed complete or partial response per 2007 International Working Group (IWG) criteria to the date of documented disease progression or death due to any cause, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. DOR was censored at the time of study withdrawal for hematopoietic stem cell transplant, or at the time of study termination, whichever was earlier, for patients whose disease was still in response.

Time frame: Up to approximately 2 years

Population: Patients who achieved a CR or PR. The study was not designed to make formal statistical comparisons of DOR between cohorts.

Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study

Time frame: Up to approximately 2 years

Population: Safety Analysis Set, defined as all enrolled patients who received at least 1 dose of study treatment.~The study was not designed to make formal statistical comparisons of AE numbers (percentages) between cohorts.

Interval of time from the start of study drug treatment to the date of death for any reason. OS was censored at the time of study withdrawal or study termination, whichever was earlier, for patients without reported death.

Time frame: Up to approximately 3 years

Population: Intent-to-Treat Analysis Set, defined as all patients who were enrolled into the trial regardless of whether or not they received study treatment.~The study was not designed to make formal statistical comparisons of OS between cohorts.

Defined as the area under the concentration-time curve from time 0 to the last measurable plasma concentration

Time frame: Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)

Population: Defined as all patients (pts) who received at least 1 dose of study drug on Cycle 1 Day 1 and had at least 1 valid PK concentration. AUC0-t data were previously generated for subset of 50 pts, 4 of whom reached Cycle 6 at time of analysis. As prespecified by the analysis plan, combination therapy cohorts were combined since AUC for small molecules should not be affected by lymphoma subtype. PK samples from remaining pts were not tested due to sponsor company closure soon after study termination.

Defined as the time required to reduce plasma concentration by 50% after study drug administration

Time frame: Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)

Population: Defined as all patients who received at least 1 dose of study drug on Cycle 1 Day 1 and had at least 2 valid PK concentrations in the terminal elimination phase. This stricter requirement explains why, for example, the overall number analyzed for t1/2 (ie, 16) is less than the overall number analyzed for the other PK parameters (ie, 50). As prespecified by the analysis plan, combination therapy cohorts were combined since t1/2 for small molecules should not be affected by lymphoma subtype.

Defined as the peak plasma concentration \[Cmax\] after study drug administration

Time frame: Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)

Population: Defined as all patients (pts) who received at least 1 dose of study drug on Cycle 1 Day 1 and had at least 1 valid PK concentration. Cmax data were previously generated for subset of 50 pts, 4 of whom reached Cycle 6 at time of analysis. As prespecified by the analysis plan, combination therapy cohorts were combined since Cmax for small molecules should not be affected by lymphoma subtype. PK samples from remaining pts were not tested due to sponsor company closure soon after study termination.

Defined as the time required to reach peak plasma concentration \[Cmax\] after study drug administration

Time frame: Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)

Population: Defined as all patients (pts) who received at least 1 dose of study drug on Cycle 1 Day 1 and had at least 1 valid PK concentration. Tmax data were previously generated for subset of 50 pts, 4 of whom reached Cycle 6 at time of analysis. As prespecified by the analysis plan, combination therapy cohorts were combined since Tmax for small molecules should not be affected by lymphoma subtype. PK samples from remaining pts were not tested due to sponsor company closure soon after study termination.

Interval of time from the start of study drug treatment to the date of first documented disease progression (defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir), initiation of new antineoplastic therapy, or death from any cause, whichever occurred first. PFS was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression or death.

Time frame: Up to approximately 3 years

Population: Intent-to-Treat Analysis Set, defined as all patients who were enrolled into the trial regardless of whether or not they received study treatment.~The study was not designed to make formal statistical comparisons of PFS between cohorts.

Interval of time from the start of study drug treatment to the date of next anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy).

Time frame: Up to approximately 3 years

Population: The clinical trial was terminated before the outcome measure data were collected (data export from the clinical database just prior to study termination retrieved from data manager files contained data listings to support determinations of other secondary efficacy outcome measures but not post-treatment anticancer therapy regimen dates to support TTNLT determination, and investigation into the cause of these uncollected data was preempted by sponsor company closure soon after study termination).

Interval of time from the start of study drug treatment to the date of disease progression, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. TTP was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression.

Time frame: Up to approximately 3 years

Population: Intent-to-Treat Analysis Set, defined as all patients who were enrolled into the trial regardless of whether or not they received study treatment.~The study was not designed to make formal statistical comparisons of TTP between cohorts.

Interval of time from date of first observed complete or partial response per 2007 International Working Group (IWG) criteria to the date of documented disease progression or death due to any cause, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. DOR was censored at the time of study withdrawal for hematopoietic stem cell transplant, or at the time of study termination, whichever was earlier, for patients whose disease was still in response.

Time frame: Up to approximately 2 years

Population: Patients who achieved a CR or PR

Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.

Time frame: Up to approximately 2 years

Population: Intent-to-Treat Analysis Set, defined as all patients who were enrolled into the trial regardless of whether or not they received study treatment.~The sum of the Overall Number of Participants Analyzed across all subgroups (ie, 57) additionally includes pre-specified ORR analyses in a subset of 14 patients in the Peripheral T-Cell Lymphoma (Combination Therapy) cohort previously treated with only 1 line of anti-lymphoma therapy.