Endometrial Cancer, Ovarian Cancer, Small Cell Lung Cancer, Soft Tissue Sarcoma, Triple-negative Breast Cancer
Conditions
Keywords
Phase 1 (P1), Solid Tumor, Small Cell Lung Cancer (SCLC), Breast Cancer, Ovarian Cancer (OC), Soft Tissue Sarcoma (STS), Relapsed/Refractory, Triple Negative, Gastrointestinal stromal tumors (GIST), Epithelial cancer, Peritoneal cancer, Fallopian tube cancer, Metastatic, Advanced, Endometrial Cancer (EC), Phase 2 (P2), Corrected QT interval (QTc), System Organ Class (SOC), Preferred Term (PT), Day 1 (D1), Day 15 (D15), Treatment-Emergent Adverse Events (TEAEs), Investigational Medicinal Product (IMP), Polymorphonuclear cell (PMN), Progressive Response (PR), Stable disease (SD), Maximum administered dose (MAD), Dose-limiting toxicity (DLT)
Brief summary
Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.
Detailed description
The study consists of 2 phases and 2 sub-studies: This study is a multi-centre, open-label phase 1/2 study of single agent EDO-S101 in subjects with advanced solid tumours. Phase 1 part of the study is designed to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the Pharmacokinetic (PK) of EDO-S101 as a single agent in patients with solid tumours who have progressed after at least one (1) line of therapy and for whom no other standard therapy with proven clinical benefit is available. Phase 2 part of the study is designed to evaluate the overall response rate (ORR) of the RP2D, plus the rate of patients with stable disease (SD) at 4 or 6 months, depending on the type of solid tumour. The RP2D was determined after phase 1 to be 80 mg/m2 of EDO-S101 administered over 1 hour on Day 1 and Day 15 of each 4-week treatment cycle. In addition, two sub-studies are designed to better characterize the effect of EDO-S101: one at a dose of 60 mg/m2 administered over 60 minutes and the second at a dose of 80 mg/m2 administered over 80 minutes on cardiac repolarization (QTc) and other ECG parameters in the subjects with solid tumours. Subjects were eligible for these studies if they had a histologically confirmed solid tumour, signed informed consent and met the inclusion/exclusion criteria. After providing informed consent, subjects were screened, and all procedures were performed as per protocol.
Interventions
DRUGTinostamustine 60mg/m2 over 30min
Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 80mg/m2 over 30min
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 100mg/m2 over 30min
Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 60mg/m2 over 60min
Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 80mg/m2 over 60min
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 100mg/m2 over 60min
Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
DRUGTinostamustine 80mg/m2 over 80min
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 80 minutes on Days (D) 1 and 15 of each 28-day cycle.
Sponsors
Mundipharma Research Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In phase 1 (dose escalation phase) of the study, subjects were allocated sequentially. In phase 2, subjects were allocated in parallel to the various arms (cohorts) based on their cancer specifics. In the substudies 1 and 2, subjects were allocated into a single group in each substudy. Overall, the study model is described as Sequential as the study proceeded in phases.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion and
Exclusion criteria
were reviewed for each potential patient during Screening. All eligible patients were treated with Tinostamustine employing sequential enrollment (i.e. as they qualify for participation). In the first phase of the trial (Phase 1), the dose received for each eligible patient was dependent on the requirements of the dose escalation scheme at the time the patient was enrolled. In the second phase of the trial (Phase 2), all patients were treated with the Tinostamustine at 80 mg/m2 administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. General Inclusion Criteria for Phase 1 and Phase 2 portions of Study: 1. Patient willing and able to sign the informed consent. 2. Patients age ≥18 years at signing the informed consent. 3. Life expectancy \> 3 months. 4. Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed following at least one line of therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. 5. Patients with secondary metastasis to the central nervous system (CNS) are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to trial day 1 and they meet all of the following criteria: 1. Residual neurological symptoms ≤Grade 1. 2. No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids providing the dose has been stable for at least 2 weeks prior to starting the trial medication. 3. Follow-up imaging studies show no progression of treated lesions and no new lesions. 6. Evaluable disease; measurable on imaging as assessed by RECIST version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 8. Absolute neutrophil count (ANC) (polymorphonuclear cells \[PMN\] plus bands) \>1,000/ μL. 9. Platelets ≥100,000 μL. Platelet transfusions within the 14 days before Day 1 of Cycle 1 is prohibited. 10. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 3 upper limit of normal (ULN). In cases with liver involvement ALT/ AST ≤ 5× ULN. 11. Total bilirubin ≤1.5 mg/dL unless elevated due to known Gilbert's syndrome. 12. Creatinine ≤1.5 ULN. 13. Serum potassium and magnesium at least at the lowest limit of normal (LLN), before every IMP administration. If it is below the LLN, supplementation is permissible. 14. Female study participants of child-bearing potential and their partners, and male study participants who intend to be sexually active with a woman of child-bearing potential, must be willing to use at least two (2) highly effective forms of contraception. This should start from the time of study enrollment and continue throughout IMP administration. For female study participants of child-bearing potential this must continue using contraception for at least six (6) months after the last administration of the IMP. Female study participants should be willing to have a pregnancy test performed at screening, ≤ 1 day prior to day 1 of each IMP administration and at study treatment discontinuation. Male study participants who are sexually active with a woman of child-bearing potential should also use a condom during treatment and for at least ninety (90) days after the last administration of IMP. Vasectomized males are considered fertile; therefore, vasectomized partners and patients must be willing to use a secondary method of effective birth control. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months. | All TEAEs was reported from the first dose of study drug through the time of study drug discontinuation (at any time or Day 28 of the last treatment Cycle). All treatment-related TEAEs was followed until resolution or stabilization. For the purpose of regulatory reporting requirements, causal relationships of definite, probable, and possible was considered treatment-related. Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03. (June 2010). |
| Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days. | The Clinical Benefit Response Rate is calculated as the number of patients with Clinical Benefit Response divided by number of patients in the FAS (in the respective cohort). Clinical Benefit Response is defined as patients achieving stable disease with a duration of at least 12 weeks (84 days). Summary subjects analysed were 36. |
| Highest Change From Baseline in QTcF in Sub-studies | From cycle 1 and at every cycle on treatment days D1 and D15, assessed pre-dose and post-start of infusion at 30 and 80mins (Substudy 2 - up to 6 months) and 30, 60, 90, 120 and 180mins (substudy 1 - up to 6 months). | QTcF: corrected QT interval \[QTc\] using Fridericia's formula) and other electrocardiogram (ECG) parameters in subjects with solid tumours who have progressed after at least 1 line of therapy and for whom no other standard therapy with proven clinical benefit is available. Within each cycle a Change from baseline (CfB) is calculated for QTcF relative to the baseline value of day 1 of the cycle. QTcF CfB= QTcF Post-dose value - QTcF pre-dose value of D1 ECG Parameters: 4-hours ECG holter monitoring in C1 and ECGs during EDO-S101 administration. Continuous variables the mean and standard deviation are presented together with the total number of observations and the number of missing and non-missing values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Time for Phase 2 and Sub Studies | From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 42 months. | Overall survival is defined as the number days between the date of the first dose of treatment and the date of death. If no date of death is recorded the Overall Survival time is censored at the Last available visit date. Phase 2: To determine the overall survival (OS) time for subjects with solid tumours. SS1:To determine the overall survival (OS) time for subjects who received 60 mg/m2 of EDO-S101 during a 60-minute Infusion. SS2: To determine the overall survival (OS) time for subjects who received 80 mg/m2 of EDO-S101 during a 80-minute Infusion. |
| Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies | From patient's first overall response of CR or PR, until disease progression/subsequent anti-cancer therapy/death from any cause, up to 24 months. | The duration of objective response is measured from the date of the first tumor response assessment with an Investigator's Overall Response of CR or PR (whichever status is recorded first) until the date of progression or death. DoR is presented by subject. |
| Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies | From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months) | To determine the objective response rate (ORR) and the clinical benefit rate (CBR \[Complete Response (CR), Partial Response (PR) plus durable Stable Disease (SD)\]) in Sub Studies. SD was regarded as durable if, after observing SD, the first observation of PD was at least 84 days after the start of study treatment. |
| Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies. | From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months). | Duration of SD, was defined as the number of days between the date of the first dose of treatment and the first date of disease progression or death. SD was regarded as durable if, after observing SD, the first observation of progression disease was at least 84 days after the start of study treatment. |
| Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15. | — |
| Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15. | — |
| Summary of Tmax in in Phase 2 and Sub Studies. | Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15. | — |
| Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15. | — |
| Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15. | — |
| Treatment-related Adverse Events on Phase 2 and Sub Studies | From each patient's time of informed consent to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 8 months | Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03, June 2010, with the exception that assessment of QTc prolongations constituting adverse events (AEs) of special interest were based on NCI CTCAE version 5.0, November 2017. All subjects who received at least 1 dose of study treatment were included in the Safety Population. Safety analyses were performed on data from all subjects in the Safety Population. Adverse events are reported on a patient basis. The percentages are calculated using the number of patients in the Safety Analysis Set as the denominator. |
| Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 26 months. | PFS was defined as the number of days between the date of the first dose of treatment of a patient and the first date of disease progression, start of a subsequent anti-cancer therapy, or death of the patient. |
Countries
Canada, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
Subjects were recruited by physicians at the study sites between Nov-2017 and Aug-2022.
Pre-assignment details
Adults with histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed during or following at least 1 previous line of therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient.
Participants by arm
| Arm | Count |
|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min). Cohort 1 Safety Population (All patients who received at least one (1) dose of study treatment at 60mg/m2 over a 30 minutes infusion time) | 3 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min). Cohort 2 Safety Population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 30 minutes infusion time) | 3 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min). Cohort 3 Safety Population (All patients who received at least one (1) dose of study treatment at 100mg/m2 over a 30 minutes infusion time) | 3 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min). Cohort 4 Safety Population (All patients who received at least one (1) dose of study treatment at 60mg/m2 over a 60 minutes infusion time) | 3 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min). Cohort 5 Safety Population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) | 8 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min). Cohort 6 Safety Population (All patients who received at least one (1) dose of study treatment at 100mg/m2 over a 60 minutes infusion time) | 2 |
| Tinostamustine (EDO-S101) - Phase 2 SCLC Safety population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) in patients with relapsed/refractory small cell lung cancer. | 4 |
| Tinostamustine (EDO-S101) - Phase 2 STS Safety population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) in patients with relapsed/refractory soft tissue sarcoma. | 10 |
| Tinostamustine (EDO-S101) - Phase 2 TNBC Safety population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) in patients with relapsed/refractory triple-negative breast cancer. | 4 |
| Tinostamustine (EDO-S101) - Phase 2 OC Safety population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) in patients with relapsed/refractory ovarian cancer. | 12 |
| Tinostamustine (EDO-S101) - Phase 2 EC Safety population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time) in patients with relapsed/refractory endometrial cancer. | 6 |
| Tinostamustine (EDO-S101) - Sub Study 1 (SS1) Subgroup treated with a dose of study treatment at 60 mg/m2 over 60 minutes infusion time. | 6 |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of study treatment at 80 mg/m2 over 80 minutes infusion time. | 7 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Do not have a post-dose tumour assessment | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 2 | 3 | 3 |
Baseline characteristics
| Characteristic | Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min). Cohort 2 | Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min). Cohort 3 | Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min). Cohort 4 | Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min). Cohort 5 | Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min). Cohort 6 | Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min). Cohort 1 | Tinostamustine (EDO-S101) - Phase 2 SCLC | Tinostamustine (EDO-S101) - Phase 2 STS | Tinostamustine (EDO-S101) - Phase 2 TNBC | Tinostamustine (EDO-S101) - Phase 2 OC | Tinostamustine (EDO-S101) - Phase 2 EC | Tinostamustine (EDO-S101) - Sub Study 1 (SS1) | Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized < 65 | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 8 Participants | 2 Participants | 8 Participants | 3 Participants | 6 Participants | 6 Participants | 48 Participants |
| Age, Customized ≥ 65 or < 75 | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 20 Participants |
| Age, Customized ≥ 75 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Customized | 60.7 years STANDARD_DEVIATION 16.2 | 61.3 years STANDARD_DEVIATION 8.74 | 54.0 years STANDARD_DEVIATION 7.55 | 61.3 years STANDARD_DEVIATION 13.55 | 56.5 years STANDARD_DEVIATION 9.19 | 61.0 years STANDARD_DEVIATION 12.12 | 62.5 years STANDARD_DEVIATION 6.56 | 53.2 years STANDARD_DEVIATION 12.51 | 62.8 years STANDARD_DEVIATION 18.39 | 61.6 years STANDARD_DEVIATION 9 | 62.0 years STANDARD_DEVIATION 8.74 | 49.5 years STANDARD_DEVIATION 9.67 | 50.6 years STANDARD_DEVIATION 17.18 | 57.87 years STANDARD_DEVIATION 12.08 |
| Body Mass Index (BMI) | 30.850 kg/m^2 STANDARD_DEVIATION 3.9493 | 27.775 kg/m^2 STANDARD_DEVIATION 3.981 | 35.970 kg/m^2 STANDARD_DEVIATION 6.1309 | 24.539 kg/m^2 STANDARD_DEVIATION 6.5699 | 32.675 kg/m^2 STANDARD_DEVIATION 11.7026 | 31.620 kg/m^2 STANDARD_DEVIATION 1.7819 | 25.148 kg/m^2 STANDARD_DEVIATION 8.6313 | 28.206 kg/m^2 STANDARD_DEVIATION 9.9631 | 24.483 kg/m^2 STANDARD_DEVIATION 4.941 | 26.616 kg/m^2 STANDARD_DEVIATION 5.7605 | 25.677 kg/m^2 STANDARD_DEVIATION 5.2798 | 36.168 kg/m^2 STANDARD_DEVIATION 11.1967 | 26.200 kg/m^2 STANDARD_DEVIATION 6.8562 | 28.048 kg/m^2 STANDARD_DEVIATION 7.7735 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 1 Participants | 7 Participants | 2 Participants | 2 Participants | 4 Participants | 7 Participants | 4 Participants | 12 Participants | 6 Participants | 4 Participants | 7 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Height | 173.6 Centimeters STANDARD_DEVIATION 8.59 | 165.5 Centimeters STANDARD_DEVIATION 24.75 | 162.3 Centimeters STANDARD_DEVIATION 13.6 | 169.7 Centimeters STANDARD_DEVIATION 16.13 | 164.8 Centimeters STANDARD_DEVIATION 6.01 | 166.6 Centimeters STANDARD_DEVIATION 12.87 | 166.6 Centimeters STANDARD_DEVIATION 12.98 | 166.3 Centimeters STANDARD_DEVIATION 7.16 | 159.1 Centimeters STANDARD_DEVIATION 6.78 | 160.3 Centimeters STANDARD_DEVIATION 6.42 | 160.4 Centimeters STANDARD_DEVIATION 3.57 | 165.4 Centimeters STANDARD_DEVIATION 11.38 | 169.5 Centimeters STANDARD_DEVIATION 10.55 | 165.07 Centimeters STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 8 Participants | 3 Participants | 10 Participants | 4 Participants | 5 Participants | 6 Participants | 57 Participants |
| Region of Enrollment Canada | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants |
| Region of Enrollment Italy | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Spain | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 8 Participants | 2 Participants | 3 Participants | 0 Participants | 9 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 7 Participants | 58 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants | 4 Participants | 12 Participants | 6 Participants | 5 Participants | 4 Participants | 52 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 19 Participants |
| Weight | 92.5 Kilograms STANDARD_DEVIATION 7.51 | 75.3 Kilograms STANDARD_DEVIATION 11.74 | 93.7 Kilograms STANDARD_DEVIATION 8.87 | 71.2 Kilograms STANDARD_DEVIATION 22.68 | 87.6 Kilograms STANDARD_DEVIATION 25.31 | 74.2 Kilograms STANDARD_DEVIATION 27.82 | 72.7 Kilograms STANDARD_DEVIATION 38.14 | 78.6 Kilograms STANDARD_DEVIATION 29.17 | 62.4 Kilograms STANDARD_DEVIATION 16.3 | 68.4 Kilograms STANDARD_DEVIATION 15.23 | 66.1 Kilograms STANDARD_DEVIATION 13.94 | 97.9 Kilograms STANDARD_DEVIATION 27.79 | 74.7 Kilograms STANDARD_DEVIATION 17.16 | 76.16 Kilograms STANDARD_DEVIATION 22.65 |
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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 2 / 8 | 0 / 2 | 1 / 4 | 3 / 10 | 2 / 4 | 2 / 12 | 3 / 6 | 4 / 6 | 2 / 7 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 8 / 8 | 2 / 2 | 4 / 4 | 10 / 10 | 4 / 4 | 12 / 12 | 6 / 6 | 6 / 6 | 6 / 7 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 2 / 3 | 3 / 3 | 5 / 8 | 2 / 2 | 0 / 4 | 6 / 10 | 1 / 4 | 7 / 12 | 4 / 6 | 6 / 6 | 0 / 7 |
Outcome results
Primary
Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2
The Clinical Benefit Response Rate is calculated as the number of patients with Clinical Benefit Response divided by number of patients in the FAS (in the respective cohort). Clinical Benefit Response is defined as patients achieving stable disease with a duration of at least 12 weeks (84 days). Summary subjects analysed were 36.
Time frame: From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days.
Population: All subjects who received at least 1 dose of study treatment were included in the Full Analysis (FA) Population. Efficacy analyses were performed on data from all subjects in the FA Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | 0 percentage of patients |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | 40.0 percentage of patients |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | 50.0 percentage of patients |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | 50.0 percentage of patients |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2 | 50.0 percentage of patients |
Primary
Highest Change From Baseline in QTcF in Sub-studies
QTcF: corrected QT interval \[QTc\] using Fridericia's formula) and other electrocardiogram (ECG) parameters in subjects with solid tumours who have progressed after at least 1 line of therapy and for whom no other standard therapy with proven clinical benefit is available. Within each cycle a Change from baseline (CfB) is calculated for QTcF relative to the baseline value of day 1 of the cycle. QTcF CfB= QTcF Post-dose value - QTcF pre-dose value of D1 ECG Parameters: 4-hours ECG holter monitoring in C1 and ECGs during EDO-S101 administration. Continuous variables the mean and standard deviation are presented together with the total number of observations and the number of missing and non-missing values.
Time frame: From cycle 1 and at every cycle on treatment days D1 and D15, assessed pre-dose and post-start of infusion at 30 and 80mins (Substudy 2 - up to 6 months) and 30, 60, 90, 120 and 180mins (substudy 1 - up to 6 months).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Highest Change From Baseline in QTcF in Sub-studies | 53.33 msec | Standard Deviation 23.777 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Highest Change From Baseline in QTcF in Sub-studies | 33.24 msec | Standard Deviation 12.588 |
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1
All TEAEs was reported from the first dose of study drug through the time of study drug discontinuation (at any time or Day 28 of the last treatment Cycle). All treatment-related TEAEs was followed until resolution or stabilization. For the purpose of regulatory reporting requirements, causal relationships of definite, probable, and possible was considered treatment-related. Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03. (June 2010).
Time frame: From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months.
Population: The safety analysis summarised TEAEs for all treated subjects using discrete summaries at the subject and event level by system organ class (SOC) and preferred term (PT). Treatment-related TEAEs were summarised similarly. TEAEs were also summarised by the grade of National Cancer Institute Common Terminology Criteria for Adverse Events. All AEs were coded using the MedDRA® version 24.0
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 5 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 8 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 6 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Nervous system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | General disorders and administration site conditions | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Gastrointestinal disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Investigations | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Skin and subcutaneous tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 | Blood and lymphatic system disorders | 1 Participants |
Secondary
Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Population: All enrolled subjects in the Safety Population with at least 1 quantifiable pre-dose and 1 quantifiable post-dose PK plasma concentration in Cycle 1 were included in the PK Population. PK analyses were performed using the PK population. 48 subjects of the Safety Population were included in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 938 ng.h/mL | Geometric Coefficient of Variation 41.9 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 40.9 ng.h/mL | Geometric Coefficient of Variation 94.1 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 943 ng.h/mL | Geometric Coefficient of Variation 53.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 5.19 ng.h/mL | Geometric Coefficient of Variation 420 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 2.32 ng.h/mL | Geometric Coefficient of Variation 9060 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 36.0 ng.h/mL | Geometric Coefficient of Variation 80.5 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 48.6 ng.h/mL | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 54.4 ng.h/mL | Geometric Coefficient of Variation 61.2 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 1680 ng.h/mL | Geometric Coefficient of Variation 22.6 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 12.4 ng.h/mL | Geometric Coefficient of Variation 1430 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 35.2 ng.h/mL | Geometric Coefficient of Variation 33.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 1390 ng.h/mL | Geometric Coefficient of Variation 28.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 53.3 ng.h/mL | Geometric Coefficient of Variation 44.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 1520 ng.h/mL | Geometric Coefficient of Variation 41.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 0.865 ng.h/mL | Geometric Coefficient of Variation 248 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 1.32 ng.h/mL | Geometric Coefficient of Variation 163 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 47.7 ng.h/mL | Geometric Coefficient of Variation 48.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 1490 ng.h/mL | Geometric Coefficient of Variation 40.9 |
Secondary
Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Population: All enrolled subjects in the Safety Population with at least 1 quantifiable pre-dose and 1 quantifiable post-dose PK plasma concentration in Cycle 1 were included in the PK Population. PK analyses were performed using the PK population. 48 subjects of the Safety Population were included in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D15 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D1 | 69800 mL/h/m^2 | Geometric Coefficient of Variation 48.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D1 | 2410000 mL/h/m^2 | Geometric Coefficient of Variation 54.2 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D15 | 89600 mL/h/m^2 | Geometric Coefficient of Variation 19.5 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D15 | 1240000 mL/h/m^2 | Geometric Coefficient of Variation 14.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D1 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D1 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D15 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D1 | 2270000 mL/h/m^2 | Geometric Coefficient of Variation 22.4 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D15 | 1740000 mL/h/m^2 | Geometric Coefficient of Variation 40.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D1 | 56000 mL/h/m^2 | Geometric Coefficient of Variation 23.9 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D15 | 49600 mL/h/m^2 | Geometric Coefficient of Variation 58.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D15 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M8 metabolite concentration, Cycle 1 D1 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D1 | 50800 mL/h/m^2 | Geometric Coefficient of Variation 41.1 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D1 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | M2 metabolite concentration, Cycle 1 D15 | NA mL/h/m^2 | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies | EDO-S101 concentration, Cycle 1 D15 | 53600 mL/h/m^2 | Geometric Coefficient of Variation 45.2 |
Secondary
Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies
The duration of objective response is measured from the date of the first tumor response assessment with an Investigator's Overall Response of CR or PR (whichever status is recorded first) until the date of progression or death. DoR is presented by subject.
Time frame: From patient's first overall response of CR or PR, until disease progression/subsequent anti-cancer therapy/death from any cause, up to 24 months.
Population: Number of participants is zero in some of the arms as no participants achieved a response of CR or PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies | 51 days |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies | 52 days |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies | 734 days |
Secondary
Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Population: All enrolled subjects in the Safety Population with at least 1 quantifiable pre-dose and 1 quantifiable post-dose PK plasma concentration in Cycle 1 were included in the PK Population. PK analyses were performed using the PK population. 48 subjects of the Safety Population were included in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D1 | 1150 nanogram(s)/millilitre | Geometric Coefficient of Variation 15.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D15 | 999 nanogram(s)/millilitre | Geometric Coefficient of Variation 38.6 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D1 | 2.18 nanogram(s)/millilitre | Geometric Coefficient of Variation 65.4 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D15 | 2.31 nanogram(s)/millilitre | Geometric Coefficient of Variation 105 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D1 | 37.4 nanogram(s)/millilitre | Geometric Coefficient of Variation 17 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D15 | 31.2 nanogram(s)/millilitre | Geometric Coefficient of Variation 46.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D15 | 24.6 nanogram(s)/millilitre | Geometric Coefficient of Variation 33.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D1 | 1210 nanogram(s)/millilitre | Geometric Coefficient of Variation 11.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D15 | 2.91 nanogram(s)/millilitre | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D1 | 27.0 nanogram(s)/millilitre | Geometric Coefficient of Variation 36.5 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D15 | 1040 nanogram(s)/millilitre | Geometric Coefficient of Variation 21.2 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D1 | 2.32 nanogram(s)/millilitre | Geometric Coefficient of Variation 65.5 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D15 | 1540 nanogram(s)/millilitre | Geometric Coefficient of Variation 41.5 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D1 | 1.92 nanogram(s)/millilitre | Geometric Coefficient of Variation 77.9 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D15 | 49.8 nanogram(s)/millilitre | Geometric Coefficient of Variation 43.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M2 metabolite concentration, Cycle 1 D15 | 1.98 nanogram(s)/millilitre | Geometric Coefficient of Variation 63.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | EDO-S101 concentration, Cycle 1 D1 | 1620 nanogram(s)/millilitre | Geometric Coefficient of Variation 43.3 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies | M8 metabolite concentration, Cycle 1 D1 | 47.7 nanogram(s)/millilitre | Geometric Coefficient of Variation 50.2 |
Secondary
Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies.
Duration of SD, was defined as the number of days between the date of the first dose of treatment and the first date of disease progression or death. SD was regarded as durable if, after observing SD, the first observation of progression disease was at least 84 days after the start of study treatment.
Time frame: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months).
Population: Analysis population includes only those subjects who achieved stable disease (SD). The Duration of SD (was regarded as durable if, after observing SD, the first observation of PD was at least 84 days after the start of study treatment) was based of number of patients with Best Overall Stable Disease Response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies. | <84 days | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies. | ≥84 days | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies. | <84 days | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies. | ≥84 days | 1 Participants |
Secondary
Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies
To determine the objective response rate (ORR) and the clinical benefit rate (CBR \[Complete Response (CR), Partial Response (PR) plus durable Stable Disease (SD)\]) in Sub Studies. SD was regarded as durable if, after observing SD, the first observation of PD was at least 84 days after the start of study treatment.
Time frame: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months)
Population: All subjects who received at least 1 dose of study treatment were included in the Full Analysis (FA) Population. Efficacy analyses were performed on data from all subjects in the FA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies | Clinical Benefit Response Rate (CR+PR+durable SD) % | 50.0 percentage of participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies | Objective Response Rate (CR+PR) (%) | 16.7 percentage of participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies | Objective Response Rate (CR+PR) (%) | 0 percentage of participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies | Clinical Benefit Response Rate (CR+PR+durable SD) % | 14.3 percentage of participants |
Secondary
Overall Survival (OS) Time for Phase 2 and Sub Studies
Overall survival is defined as the number days between the date of the first dose of treatment and the date of death. If no date of death is recorded the Overall Survival time is censored at the Last available visit date. Phase 2: To determine the overall survival (OS) time for subjects with solid tumours. SS1:To determine the overall survival (OS) time for subjects who received 60 mg/m2 of EDO-S101 during a 60-minute Infusion. SS2: To determine the overall survival (OS) time for subjects who received 80 mg/m2 of EDO-S101 during a 80-minute Infusion.
Time frame: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 42 months.
Population: Full Analysis Set (FAS): All patients who received at least 1 dose of trial treatment and had at least 1 post-baseline response evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 114.5 Days |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 346.5 Days |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 218.5 Days |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 261.0 Days |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 127.0 Days |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Overall Survival (OS) Time for Phase 2 and Sub Studies | 177.0 Days |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Overall Survival (OS) Time for Phase 2 and Sub Studies | 139.0 Days |
Secondary
Progression Free Survival (PFS) Time for Phase 2 and Sub Studies
PFS was defined as the number of days between the date of the first dose of treatment of a patient and the first date of disease progression, start of a subsequent anti-cancer therapy, or death of the patient.
Time frame: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 26 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 54.0 days |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 56.0 days |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 85.0 days |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 63.0 days |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 87.0 days |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 177.0 days |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Progression Free Survival (PFS) Time for Phase 2 and Sub Studies | 65.0 days |
Secondary
Summary of Half-life of Tinostamustine in Phase 2 and Substudies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Population: All enrolled subjects in the Safety Population with at least 1 quantifiable pre-dose and 1 quantifiable post-dose PK plasma concentration in Cycle 1 were included in the PK Population. PK analyses were performed using the PK population. 48 subjects of the Safety Population were included in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D15 | 2.30 hour | Geometric Coefficient of Variation 153 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D1 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D1 | 0.602 hour | Geometric Coefficient of Variation 30.2 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D1 | 0.919 hour | Geometric Coefficient of Variation 38 |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D15 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D15 | 0.678 hour | Geometric Coefficient of Variation 45.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D15 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D1 | 1.22 hour | Geometric Coefficient of Variation 96.8 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D15 | 4.03 hour | Geometric Coefficient of Variation 2150 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D15 | 2.48 hour | Geometric Coefficient of Variation 99.7 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D1 | 2.14 hour | Geometric Coefficient of Variation 185 |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D1 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D15 | 4.43 hour | Geometric Coefficient of Variation 553 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D1 | 0.70 hour | Geometric Coefficient of Variation 54 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | EDO-S101 concentration, Cycle 1 D15 | 0.704 hour | Geometric Coefficient of Variation 51.2 |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D1 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M2 metabolite concentration, Cycle 1 D15 | NA hour | — |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Half-life of Tinostamustine in Phase 2 and Substudies. | M8 metabolite concentration, Cycle 1 D1 | 0.414 hour | Geometric Coefficient of Variation 49 |
Secondary
Summary of Tmax in in Phase 2 and Sub Studies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Population: All enrolled subjects in the Safety Population with at least 1 quantifiable pre-dose and 1 quantifiable post-dose PK plasma concentration in Cycle 1 were included in the PK Population. PK analyses were performed using the PK population. 48 subjects of the Safety Population were included in the PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 1 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 1 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 3.50 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 1 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 1 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 1.58 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 1.33 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 0.875 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D15 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D15 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D1 | 1.00 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | M2 metabolite concentration, Cycle 1 D15 | 1.00 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | M8 metabolite concentration, Cycle 1 D1 | 0.750 hours |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Summary of Tmax in in Phase 2 and Sub Studies. | EDO-S101 concentration, Cycle 1 D1 | 0.750 hours |
Secondary
Treatment-related Adverse Events on Phase 2 and Sub Studies
Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03, June 2010, with the exception that assessment of QTc prolongations constituting adverse events (AEs) of special interest were based on NCI CTCAE version 5.0, November 2017. All subjects who received at least 1 dose of study treatment were included in the Safety Population. Safety analyses were performed on data from all subjects in the Safety Population. Adverse events are reported on a patient basis. The percentages are calculated using the number of patients in the Safety Analysis Set as the denominator.
Time frame: From each patient's time of informed consent to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 8 months
Population: The safety analysis summarised TEAEs for all treated subjects using discrete summaries at the subject and event level by system organ class (SOC) and preferred term (PT). Treatment-related TEAEs were summarised similarly. TEAEs were also summarised by the grade of National Cancer Institute Common Terminology Criteria for Adverse Events. All AEs were coded using the MedDRA® version 24.0
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 8 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 12 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 7 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 9 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 4 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 5 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 5 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 3 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Metabolism and nutrition disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Investigations | 2 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Musculoskeletal and connective tissue disorders | 1 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | General disorders and administration site conditions | 1 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Vascular disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Injury, poisoning and procedural complications | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Nervous system disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Blood and lymphatic system disorders | 3 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Cardiac disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Skin and subcutaneous tissue disorders | 0 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Gastrointestinal disorders | 2 Participants |
| Tinostamustine (EDO-S101) - Sub Study 2 (SS2) | Treatment-related Adverse Events on Phase 2 and Sub Studies | Infections and infestations | 2 Participants |