EBV Related Carcinoma, EBV-Related Gastric Carcinoma, EBV-Related Leiomyosarcoma, EBV-Related Sarcoma, Nasopharyngeal Carcinoma
Conditions
Brief summary
This study will evaluate the safety and efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive solid tumors and in combination with pembrolizumab in patients with recurrent/metastatic nasopharyngeal carcinoma
Detailed description
This is an open-label, multicenter Phase 1b/2 study evaluating nanatinostat in combination with valganciclovir alone and in combination with pembrolizumab. Nanatinostat is a selective class I HDAC inhibitor which induces EBV early lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) in patients with EBV+ RM-NPC followed by a Project Optimus \| FDA (https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus) cohort to confirm the RP2D. Up to 60 patients with EBV+ RM-NPC will be randomized 1:1 to receive nanatinostat in combination with valganciclovir at the confirmed RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers in the Phase 2 dose expansion part of the study. Additionally, patients with other EBV+ solid tumors will be enrolled to receive nanatinostat in combination with valganciclovir at the RP2D in a Phase 1b cohort. The study was prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.
Interventions
DRUGNanatinostat
Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, then Phase 2: Nanatinostat at the confirmed recommended Phase 2 dose
DRUGValganciclovir
Phase 1b: Valganciclovir starting at 900 mg orally daily, then Phase 2: Valganciclovir at the confirmed recommended Phase 2 dose
DRUGPembrolizumab
Phase 2: Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks
Sponsors
Viracta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A traditional 3+3 dose escalation design followed first by a dose optimization cohort and then by dose expansion with 1:1 randomization to receive nanatinostat and valganciclovir with or without pembrolizumab in Phase 2. The study was prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Recurrent or metastatic EBV+ nasopharyngeal carcinoma (RM-NPC) for whom no potentially curative options are available, who have received at least 1 prior line of platinum-based chemotherapy and no more than 3 prior lines of therapy for RM-NPC. * Phase 1b exploratory proof-of-concept cohort only: Advanced/metastatic EBV+ non-NPC solid tumors with no available curative therapies. * Measurable disease per RECIST v1.1 * ECOG performance status 0 or 1 * Adequate bone marrow and liver function Key
Exclusion criteria
* Anti-tumor treatment with cytotoxic drugs, biologic therapy, immunotherapy, or other investigational drugs within 4 weeks or \>5 half-lives, whichever is shorter * Active CNS disease * Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir * Active infection requiring systemic therapy * Active autoimmune disease that has required systemic therapy with modifying agents, corticosteroids, or immunosuppressive agents * Positive hepatitis B or hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | DLT period of 28 days | Percentage of patients experiencing a DLT, defined as an adverse event or clinically significant abnormal laboratory value that is at least possibly related to study drugs and is not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness |
| Phase 2: Overall Response Rate (ORR) | Approximately 3 years | Percentage of patients with a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Disease Control Rate (DCR) | Approximately 3 years | Percentage of patients having a CR, PR, or stable disease at any time during treatment |
| Phase 2: Progression-Free Survival (PFS) | Approximately 3 years | Interval of time from the start of study drug treatment to the date of first documented disease progression or death from any cause, whichever occurs first |
| Phase 2: Overall Survival (OS) | Approximately 3 years | Interval of time from the start of study drug treatment to date of death for any reason |
| Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | Approximately 28 days following enrollment | Defined as the time required to reach peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | Approximately 28 days following enrollment | Defined as the time required to reach peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1 |
| Incidence of Adverse Events | Approximately 3 years | Percentage of patients experiencing at least one treatment-emergent adverse event (AE), defined as those AEs with onset after the first dose of study drug or existing events that worsened after the first dose during the study |
| Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | Approximately 28 days following enrollment | Defined as the peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | Approximately 28 days following enrollment | Defined as the area under the concentration-time curve from time 0 to the last measurable nanatinostat concentration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | Approximately 28 days following enrollment | Defined as the area under the concentration-time curve from time 0 to the last measurable ganciclovir concentration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | Approximately 28 days following enrollment | Defined as the time required to reduce nanatinostat plasma concentration by 50% after nanatinostat administration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | Approximately 28 days following enrollment | Defined as the time required to reduce ganciclovir plasma concentration by 50% after valganciclovir administration on Cycle 2 Day 1 |
| Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | Approximately 28 days following enrollment | Defined as the peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1 |
| Phase 2: Duration of Response (DOR) | Approximately 3 years | Interval of time from the date of first observed CR or PR to the date of documented disease progression or death due to any cause, whichever occurs first |
Countries
Australia, Canada, Hong Kong, Malaysia, Singapore, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Cohort 1 Nanatinostat 20 mg once daily, Days 1-4/week Valganciclovir 900 mg once daily | 3 |
| Dose Cohort 2 Nanatinostat 30 mg once daily, Days 1-4/week Valganciclovir 900 mg once daily | 4 |
| Dose Cohort 3 Nanatinostat 40 mg once daily, Days 1-4/week Valganciclovir 900 mg once daily | 3 |
| Dose Cohort 4 Nanatinostat 10 mg and 10 mg divided dose, Days 1-4/week Valganciclovir 900 mg twice daily x 21 days then once daily | 3 |
| Dose Cohort 5 Nanatinostat 20 mg and 10 mg divided dose, Days 1-4/week Valganciclovir 900 mg twice daily x 21 days then once daily | 4 |
| Dose Cohort 6 Nanatinostat 20 mg and 20 mg divided dose, Days 1-7/week Valganciclovir 450 mg twice daily | 3 |
| Dose Cohort 7 Nanatinostat 20 mg and 10 mg divided dose, Days 1-7/week Valganciclovir 450 mg twice daily | 6 |
| Total | 26 |
Baseline characteristics
| Characteristic | Dose Cohort 1 | Dose Cohort 2 | Dose Cohort 3 | Dose Cohort 4 | Dose Cohort 5 | Dose Cohort 6 | Dose Cohort 7 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43 Years | 52 Years | 42 Years | 54 Years | 51 Years | 48 Years | 55 Years | 50 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 21 Participants |
| Tumor Type EBV+ Nasopharyngeal Carcinoma | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 6 Participants | 26 Participants |
| Tumor Type Other EBV+ Cancer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 | 1 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 4 | 2 / 3 | 0 / 3 | 2 / 4 | 3 / 3 | 6 / 6 |
Outcome results
Primary
Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)
Percentage of patients experiencing a DLT, defined as an adverse event or clinically significant abnormal laboratory value that is at least possibly related to study drugs and is not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness
Time frame: DLT period of 28 days
Population: Phase 1b safety analysis population, defined as all patients with recurrent or metastatic EBV+ nasopharyngeal carcinoma who received at least one dose of study treatment in Phase 1b
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Cohort 1 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Dose Cohort 2 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Dose Cohort 3 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Dose Cohort 4 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Dose Cohort 5 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Dose Cohort 6 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Dose Cohort 7 | Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 2: Overall Response Rate (ORR)
Percentage of patients with a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1)
Time frame: Approximately 3 years
Population: The clinical trial was terminated before participants were enrolled in Phase 2
Secondary
Incidence of Adverse Events
Percentage of patients experiencing at least one treatment-emergent adverse event (AE), defined as those AEs with onset after the first dose of study drug or existing events that worsened after the first dose during the study
Time frame: Approximately 3 years
Population: Safety analysis population, defined as all patients who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Cohort 1 | Incidence of Adverse Events | 3 Participants |
| Dose Cohort 2 | Incidence of Adverse Events | 4 Participants |
| Dose Cohort 3 | Incidence of Adverse Events | 3 Participants |
| Dose Cohort 4 | Incidence of Adverse Events | 3 Participants |
| Dose Cohort 5 | Incidence of Adverse Events | 4 Participants |
| Dose Cohort 6 | Incidence of Adverse Events | 3 Participants |
| Dose Cohort 7 | Incidence of Adverse Events | 6 Participants |
Secondary
Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t]
Defined as the area under the concentration-time curve from time 0 to the last measurable ganciclovir concentration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of valganciclovir on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 37200 ng*h/mL | Geometric Coefficient of Variation 36.9 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 46700 ng*h/mL | Geometric Coefficient of Variation 12.1 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 30900 ng*h/mL | Geometric Coefficient of Variation 106 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 44400 ng*h/mL | Geometric Coefficient of Variation 24.8 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 38200 ng*h/mL | Geometric Coefficient of Variation 13.6 |
Secondary
Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2]
Defined as the time required to reduce ganciclovir plasma concentration by 50% after valganciclovir administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of valganciclovir on Cycle 2 Day 1 and had at least 2 valid PK concentrations in the terminal elimination phase. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | 6.88 hours | Standard Deviation 0.115 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | 7.18 hours | Standard Deviation 1.48 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | 5.64 hours | Standard Deviation 2.08 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | 5.74 hours | Standard Deviation 0.601 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2] | 6.07 hours | Standard Deviation 1.55 |
Secondary
Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax]
Defined as the peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of valganciclovir on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | 4420 ng/mL | Geometric Coefficient of Variation 3.49 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | 5860 ng/mL | Geometric Coefficient of Variation 32.1 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | 5210 ng/mL | Geometric Coefficient of Variation 80.9 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | 7580 ng/mL | Geometric Coefficient of Variation 32.6 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax] | 4860 ng/mL | Geometric Coefficient of Variation 27.2 |
Secondary
Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax]
Defined as the time required to reach peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of valganciclovir on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
| Dose Cohort 2 | Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
| Dose Cohort 3 | Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
| Dose Cohort 4 | Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
| Dose Cohort 5 | Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
Secondary
Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t]
Defined as the area under the concentration-time curve from time 0 to the last measurable nanatinostat concentration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of nanatinostat on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 362 ng*h/mL | Geometric Coefficient of Variation 82.2 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 751 ng*h/mL | Geometric Coefficient of Variation 12.7 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 896 ng*h/mL | Geometric Coefficient of Variation 39 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 416 ng*h/mL | Geometric Coefficient of Variation 12.3 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t] | 465 ng*h/mL | Geometric Coefficient of Variation 67.2 |
Secondary
Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2]
Defined as the time required to reduce nanatinostat plasma concentration by 50% after nanatinostat administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of nanatinostat on Cycle 2 Day 1 and had at least 2 valid PK concentrations in the terminal elimination phase. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | 2.11 hours | Standard Deviation 0.136 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | 1.43 hours | Standard Deviation 0.149 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | 2.64 hours | Standard Deviation 1.9 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | 2.76 hours | Standard Deviation 0 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2] | 5.29 hours | Standard Deviation 0 |
Secondary
Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax]
Defined as the peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of nanatinostat on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | 136 ng/mL | Geometric Coefficient of Variation 137 |
| Dose Cohort 2 | Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | 391 ng/mL | Geometric Coefficient of Variation 26.7 |
| Dose Cohort 3 | Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | 214 ng/mL | Geometric Coefficient of Variation 44.8 |
| Dose Cohort 4 | Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | 96.1 ng/mL | Geometric Coefficient of Variation 33.2 |
| Dose Cohort 5 | Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax] | 110 ng/mL | Geometric Coefficient of Variation 53.8 |
Secondary
Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax]
Defined as the time required to reach peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1
Time frame: Approximately 28 days following enrollment
Population: PK analysis population, defined as all patients who received at least 1 dose of nanatinostat on Cycle 2 Day 1 and had at least 1 valid PK concentration. The clinical trial was terminated before the outcome measure data were collected for Dose Cohort 6 and Dose Cohort 7.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Cohort 1 | Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | 2 hours |
| Dose Cohort 2 | Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | 1 hours |
| Dose Cohort 3 | Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | 1 hours |
| Dose Cohort 4 | Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | 4 hours |
| Dose Cohort 5 | Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax] | 7 hours |
Secondary
Phase 2: Disease Control Rate (DCR)
Percentage of patients having a CR, PR, or stable disease at any time during treatment
Time frame: Approximately 3 years
Population: The clinical trial was terminated before participants were enrolled in Phase 2
Secondary
Phase 2: Duration of Response (DOR)
Interval of time from the date of first observed CR or PR to the date of documented disease progression or death due to any cause, whichever occurs first
Time frame: Approximately 3 years
Population: The clinical trial was terminated before participants were enrolled in Phase 2
Secondary
Phase 2: Overall Survival (OS)
Interval of time from the start of study drug treatment to date of death for any reason
Time frame: Approximately 3 years
Population: The clinical trial was terminated before participants were enrolled in Phase 2
Secondary
Phase 2: Progression-Free Survival (PFS)
Interval of time from the start of study drug treatment to the date of first documented disease progression or death from any cause, whichever occurs first
Time frame: Approximately 3 years
Population: The clinical trial was terminated before participants were enrolled in Phase 2