Trial Outcomes & Findings for Study of the Safety, Pharmacokinetics and Efficacy of Tinostamustine in Patients With Advanced Solid Tumors. (NCT NCT03345485)

Last Updated: 2024-10-21

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

71 participants

Primary outcome timeframe

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.

Results posted on

2024-10-21

Participant Flow

Subjects were recruited by physicians at the study sites between Nov-2017 and Aug-2022.

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.

Participant milestones

Participant milestones
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min). Cohort 1 This is dose level 1 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 60mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min). Cohort 2 This is dose level 2 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 80mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min). Cohort 3. This is dose level 3 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 100mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. In the 30-minute infusion study drug dosing had to be delayed in subsequent cycles due to thrombocytopenia, which was associated with an extremely high Cmax of Tinostamustine. To ensure that subjects continue the study treatment safely, the Sponsor decided to stop the investigation of the 30-minute infusion time and open cohorts with the 60-minute infusion in 3 subjects with relapse/refractory solid tumors.	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min). Cohort 4 This is dose level 4 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 60mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min). Cohort 5 This is dose level 5 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min). Cohort 6 This is dose level 6 of the dose escalation phase (Phase 1) of the study. DLT of electrocardiogram QTc prolongation occurred 1 patient. Considering the DLT observed in this cohort and the rapid occurrence of treatment-induced thrombocytopenia (not meeting the DLT definitions), the SRC concluded as follows: * The dose of 100 mg/m2 was determined the MAD. * The dose level of 80 mg/m2 given i.v. over 60 minutes was determined to be the MTD * The dose level of 80 mg/m2 given i.v. over 60 minutes on Day 1 and Day 15 of each 4-week treatment cycle was determined to be the RP2D.	Tinostamustine (EDO-S101) - Phase 2 SCLC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 STS Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 TNBC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 OC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 EC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Substudy 1 Tinostamustine at dose of 60mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Substudy 2 Tinostamustine at dose of 80mg/m2 administered i.v. over 80min on D1 and D15 of each 4-week cycle.
Overall Study STARTED	3	3	3	3	8	2	4	10	4	12	6	6	7
Overall Study COMPLETED	3	3	3	3	8	2	3	8	4	12	4	3	4
Overall Study NOT COMPLETED	0	0	0	0	0	0	1	2	0	0	2	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min). Cohort 1 This is dose level 1 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 60mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min). Cohort 2 This is dose level 2 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 80mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min). Cohort 3. This is dose level 3 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 100mg/m2 administered i.v. over 30min on D1 and D15 of each 4-week cycle. In the 30-minute infusion study drug dosing had to be delayed in subsequent cycles due to thrombocytopenia, which was associated with an extremely high Cmax of Tinostamustine. To ensure that subjects continue the study treatment safely, the Sponsor decided to stop the investigation of the 30-minute infusion time and open cohorts with the 60-minute infusion in 3 subjects with relapse/refractory solid tumors.	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min). Cohort 4 This is dose level 4 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 60mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min). Cohort 5 This is dose level 5 of the dose escalation phase (Phase 1) of the study. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle. The decision to escalate to the next dose level occurred after all 3 subjects completed the Dose-limiting toxicity (DLT) observation time and were evaluated for safety and toxicity.	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min). Cohort 6 This is dose level 6 of the dose escalation phase (Phase 1) of the study. DLT of electrocardiogram QTc prolongation occurred 1 patient. Considering the DLT observed in this cohort and the rapid occurrence of treatment-induced thrombocytopenia (not meeting the DLT definitions), the SRC concluded as follows: * The dose of 100 mg/m2 was determined the MAD. * The dose level of 80 mg/m2 given i.v. over 60 minutes was determined to be the MTD * The dose level of 80 mg/m2 given i.v. over 60 minutes on Day 1 and Day 15 of each 4-week treatment cycle was determined to be the RP2D.	Tinostamustine (EDO-S101) - Phase 2 SCLC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 STS Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 TNBC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 OC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Phase 2 EC Cohort. Tinostamustine at dose of 80mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Substudy 1 Tinostamustine at dose of 60mg/m2 administered i.v. over 60min on D1 and D15 of each 4-week cycle.	Tinostamustine (EDO-S101) - Substudy 2 Tinostamustine at dose of 80mg/m2 administered i.v. over 80min on D1 and D15 of each 4-week cycle.
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

During screening visit height was recorded for 69 patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min). Cohort 1 n=3 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 60mg/m2 over a 30 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min). Cohort 2 n=3 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 30 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min). Cohort 3 n=3 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 100mg/m2 over a 30 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min). Cohort 4 n=3 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 60mg/m2 over a 60 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min). Cohort 5 n=8 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 80mg/m2 over a 60 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min). Cohort 6 n=2 Participants Safety Population (All patients who received at least one (1) dose of study treatment at 100mg/m2 over a 60 minutes infusion time)	Tinostamustine (EDO-S101) - Phase 2 SCLC n=4 Participants 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.	Tinostamustine (EDO-S101) - Phase 2 STS n=10 Participants 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.	Tinostamustine (EDO-S101) - Phase 2 TNBC n=4 Participants 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.	Tinostamustine (EDO-S101) - Phase 2 OC n=12 Participants 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.	Tinostamustine (EDO-S101) - Phase 2 EC n=6 Participants 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.	Tinostamustine (EDO-S101) - Sub Study 1 (SS1) n=6 Participants Subgroup treated with a dose of study treatment at 60 mg/m2 over 60 minutes infusion time.	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) n=7 Participants Subgroup treated with a dose of study treatment at 80 mg/m2 over 80 minutes infusion time.	Total n=71 Participants Total of all reporting groups
Age, Customized < 65	1 Participants n=3 Participants	1 Participants n=3 Participants	2 Participants n=3 Participants	3 Participants n=3 Participants	4 Participants n=8 Participants	2 Participants n=2 Participants	2 Participants n=4 Participants	8 Participants n=10 Participants	2 Participants n=4 Participants	8 Participants n=12 Participants	3 Participants n=6 Participants	6 Participants n=6 Participants	6 Participants n=7 Participants	48 Participants n=71 Participants
Age, Customized ≥ 65 or < 75	2 Participants n=3 Participants	2 Participants n=3 Participants	1 Participants n=3 Participants	0 Participants n=3 Participants	4 Participants n=8 Participants	0 Participants n=2 Participants	2 Participants n=4 Participants	2 Participants n=10 Participants	1 Participants n=4 Participants	3 Participants n=12 Participants	3 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	20 Participants n=71 Participants
Age, Customized ≥ 75	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	1 Participants n=4 Participants	1 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=7 Participants	3 Participants n=71 Participants
Age, Customized	61.0 years STANDARD_DEVIATION 12.12 • n=3 Participants	60.7 years STANDARD_DEVIATION 16.20 • n=3 Participants	61.3 years STANDARD_DEVIATION 8.74 • n=3 Participants	54.0 years STANDARD_DEVIATION 7.55 • n=3 Participants	61.3 years STANDARD_DEVIATION 13.55 • n=8 Participants	56.5 years STANDARD_DEVIATION 9.19 • n=2 Participants	62.5 years STANDARD_DEVIATION 6.56 • n=4 Participants	53.2 years STANDARD_DEVIATION 12.51 • n=10 Participants	62.8 years STANDARD_DEVIATION 18.39 • n=4 Participants	61.6 years STANDARD_DEVIATION 9.00 • n=12 Participants	62.0 years STANDARD_DEVIATION 8.74 • n=6 Participants	49.5 years STANDARD_DEVIATION 9.67 • n=6 Participants	50.6 years STANDARD_DEVIATION 17.18 • n=7 Participants	57.87 years STANDARD_DEVIATION 12.08 • n=71 Participants
Sex: Female, Male Female	2 Participants n=3 Participants	1 Participants n=3 Participants	2 Participants n=3 Participants	2 Participants n=3 Participants	4 Participants n=8 Participants	2 Participants n=2 Participants	2 Participants n=4 Participants	6 Participants n=10 Participants	4 Participants n=4 Participants	12 Participants n=12 Participants	6 Participants n=6 Participants	5 Participants n=6 Participants	4 Participants n=7 Participants	52 Participants n=71 Participants
Sex: Female, Male Male	1 Participants n=3 Participants	2 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=3 Participants	4 Participants n=8 Participants	0 Participants n=2 Participants	2 Participants n=4 Participants	4 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants	3 Participants n=7 Participants	19 Participants n=71 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=3 Participants	1 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	2 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	6 Participants n=71 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=3 Participants	3 Participants n=3 Participants	3 Participants n=3 Participants	1 Participants n=3 Participants	7 Participants n=8 Participants	2 Participants n=2 Participants	4 Participants n=4 Participants	7 Participants n=10 Participants	4 Participants n=4 Participants	12 Participants n=12 Participants	6 Participants n=6 Participants	4 Participants n=6 Participants	7 Participants n=7 Participants	62 Participants n=71 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	1 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	2 Participants n=6 Participants	0 Participants n=7 Participants	3 Participants n=71 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=71 Participants
Race (NIH/OMB) Asian	0 Participants n=3 Participants	1 Participants n=3 Participants	2 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	2 Participants n=10 Participants	0 Participants n=4 Participants	2 Participants n=12 Participants	2 Participants n=6 Participants	1 Participants n=6 Participants	0 Participants n=7 Participants	12 Participants n=71 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=71 Participants
Race (NIH/OMB) Black or African American	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	1 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=7 Participants	2 Participants n=71 Participants
Race (NIH/OMB) White	3 Participants n=3 Participants	2 Participants n=3 Participants	1 Participants n=3 Participants	3 Participants n=3 Participants	6 Participants n=8 Participants	2 Participants n=2 Participants	4 Participants n=4 Participants	8 Participants n=10 Participants	3 Participants n=4 Participants	10 Participants n=12 Participants	4 Participants n=6 Participants	5 Participants n=6 Participants	6 Participants n=7 Participants	57 Participants n=71 Participants
Race (NIH/OMB) More than one race	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=71 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	0 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=71 Participants
Region of Enrollment Canada	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	2 Participants n=4 Participants	1 Participants n=10 Participants	0 Participants n=4 Participants	4 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	7 Participants n=71 Participants
Region of Enrollment United States	3 Participants n=3 Participants	3 Participants n=3 Participants	3 Participants n=3 Participants	3 Participants n=3 Participants	8 Participants n=8 Participants	2 Participants n=2 Participants	0 Participants n=4 Participants	9 Participants n=10 Participants	4 Participants n=4 Participants	4 Participants n=12 Participants	6 Participants n=6 Participants	6 Participants n=6 Participants	7 Participants n=7 Participants	58 Participants n=71 Participants
Region of Enrollment Italy	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	2 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	3 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	5 Participants n=71 Participants
Region of Enrollment Spain	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=10 Participants	0 Participants n=4 Participants	1 Participants n=12 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	1 Participants n=71 Participants
Height	166.6 Centimeters STANDARD_DEVIATION 12.87 • n=2 Participants • During screening visit height was recorded for 69 patients	173.6 Centimeters STANDARD_DEVIATION 8.59 • n=3 Participants • During screening visit height was recorded for 69 patients	165.5 Centimeters STANDARD_DEVIATION 24.75 • n=2 Participants • During screening visit height was recorded for 69 patients	162.3 Centimeters STANDARD_DEVIATION 13.60 • n=3 Participants • During screening visit height was recorded for 69 patients	169.7 Centimeters STANDARD_DEVIATION 16.13 • n=8 Participants • During screening visit height was recorded for 69 patients	164.8 Centimeters STANDARD_DEVIATION 6.01 • n=2 Participants • During screening visit height was recorded for 69 patients	166.6 Centimeters STANDARD_DEVIATION 12.98 • n=4 Participants • During screening visit height was recorded for 69 patients	166.3 Centimeters STANDARD_DEVIATION 7.16 • n=10 Participants • During screening visit height was recorded for 69 patients	159.1 Centimeters STANDARD_DEVIATION 6.78 • n=4 Participants • During screening visit height was recorded for 69 patients	160.3 Centimeters STANDARD_DEVIATION 6.42 • n=12 Participants • During screening visit height was recorded for 69 patients	160.4 Centimeters STANDARD_DEVIATION 3.57 • n=6 Participants • During screening visit height was recorded for 69 patients	165.4 Centimeters STANDARD_DEVIATION 11.38 • n=6 Participants • During screening visit height was recorded for 69 patients	169.5 Centimeters STANDARD_DEVIATION 10.55 • n=7 Participants • During screening visit height was recorded for 69 patients	165.07 Centimeters STANDARD_DEVIATION 10.30 • n=69 Participants • During screening visit height was recorded for 69 patients
Weight	74.2 Kilograms STANDARD_DEVIATION 27.82 • n=3 Participants • During screening visit weight was recorded for 70 patients	92.5 Kilograms STANDARD_DEVIATION 7.51 • n=3 Participants • During screening visit weight was recorded for 70 patients	75.3 Kilograms STANDARD_DEVIATION 11.74 • n=2 Participants • During screening visit weight was recorded for 70 patients	93.7 Kilograms STANDARD_DEVIATION 8.87 • n=3 Participants • During screening visit weight was recorded for 70 patients	71.2 Kilograms STANDARD_DEVIATION 22.68 • n=8 Participants • During screening visit weight was recorded for 70 patients	87.6 Kilograms STANDARD_DEVIATION 25.31 • n=2 Participants • During screening visit weight was recorded for 70 patients	72.7 Kilograms STANDARD_DEVIATION 38.14 • n=4 Participants • During screening visit weight was recorded for 70 patients	78.6 Kilograms STANDARD_DEVIATION 29.17 • n=10 Participants • During screening visit weight was recorded for 70 patients	62.4 Kilograms STANDARD_DEVIATION 16.30 • n=4 Participants • During screening visit weight was recorded for 70 patients	68.4 Kilograms STANDARD_DEVIATION 15.23 • n=12 Participants • During screening visit weight was recorded for 70 patients	66.1 Kilograms STANDARD_DEVIATION 13.94 • n=6 Participants • During screening visit weight was recorded for 70 patients	97.9 Kilograms STANDARD_DEVIATION 27.79 • n=6 Participants • During screening visit weight was recorded for 70 patients	74.7 Kilograms STANDARD_DEVIATION 17.16 • n=7 Participants • During screening visit weight was recorded for 70 patients	76.16 Kilograms STANDARD_DEVIATION 22.65 • n=70 Participants • During screening visit weight was recorded for 70 patients
Body Mass Index (BMI)	31.620 kg/m^2 STANDARD_DEVIATION 1.7819 • n=2 Participants • During screening visit BMI was recorded for 69 patients	30.850 kg/m^2 STANDARD_DEVIATION 3.9493 • n=3 Participants • During screening visit BMI was recorded for 69 patients	27.775 kg/m^2 STANDARD_DEVIATION 3.9810 • n=2 Participants • During screening visit BMI was recorded for 69 patients	35.970 kg/m^2 STANDARD_DEVIATION 6.1309 • n=3 Participants • During screening visit BMI was recorded for 69 patients	24.539 kg/m^2 STANDARD_DEVIATION 6.5699 • n=8 Participants • During screening visit BMI was recorded for 69 patients	32.675 kg/m^2 STANDARD_DEVIATION 11.7026 • n=2 Participants • During screening visit BMI was recorded for 69 patients	25.148 kg/m^2 STANDARD_DEVIATION 8.6313 • n=4 Participants • During screening visit BMI was recorded for 69 patients	28.206 kg/m^2 STANDARD_DEVIATION 9.9631 • n=10 Participants • During screening visit BMI was recorded for 69 patients	24.483 kg/m^2 STANDARD_DEVIATION 4.9410 • n=4 Participants • During screening visit BMI was recorded for 69 patients	26.616 kg/m^2 STANDARD_DEVIATION 5.7605 • n=12 Participants • During screening visit BMI was recorded for 69 patients	25.677 kg/m^2 STANDARD_DEVIATION 5.2798 • n=6 Participants • During screening visit BMI was recorded for 69 patients	36.168 kg/m^2 STANDARD_DEVIATION 11.1967 • n=6 Participants • During screening visit BMI was recorded for 69 patients	26.200 kg/m^2 STANDARD_DEVIATION 6.8562 • n=7 Participants • During screening visit BMI was recorded for 69 patients	28.048 kg/m^2 STANDARD_DEVIATION 7.7735 • n=69 Participants • During screening visit BMI was recorded for 69 patients

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=3 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=3 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=3 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 n=3 Participants Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 n=8 Participants Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 n=2 Participants Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Investigations	3 Participants	3 Participants	3 Participants	3 Participants	6 Participants	2 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Gastrointestinal disorders	3 Participants	3 Participants	2 Participants	1 Participants	8 Participants	2 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Blood and lymphatic system disorders	1 Participants	3 Participants	2 Participants	3 Participants	4 Participants	1 Participants	—
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	2 Participants	2 Participants	2 Participants	5 Participants	1 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Nervous system disorders	1 Participants	1 Participants	2 Participants	1 Participants	3 Participants	2 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Skin and subcutaneous tissue disorders	1 Participants	2 Participants	1 Participants	1 Participants	2 Participants	0 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Metabolism and nutrition disorders	1 Participants	0 Participants	0 Participants	1 Participants	3 Participants	1 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Injury, poisoning and procedural complications	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Respiratory, thoracic and mediastinal disorders	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Cardiac disorders	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Musculoskeletal and connective tissue disorders	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 Vascular disorders	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=4 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=10 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=4 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 n=12 Participants Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 n=6 Participants Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2	0 percentage of patients Interval 0.0 to 52.7	40.0 percentage of patients Interval 15.0 to 69.6	50.0 percentage of patients Interval 9.8 to 90.2	50.0 percentage of patients Interval 24.5 to 75.5	50.0 percentage of patients Interval 15.3 to 84.7	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=6 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=7 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Highest Change From Baseline in QTcF in Sub-studies	53.33 msec Standard Deviation 23.777	33.24 msec Standard Deviation 12.588	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=4 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=10 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=4 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 n=12 Participants Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 n=6 Participants Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 n=6 Participants Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) n=7 Participants Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Treatment-related Adverse Events on Phase 2 and Sub Studies Nervous system disorders	2 Participants	2 Participants	0 Participants	3 Participants	3 Participants	1 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Gastrointestinal disorders	2 Participants	4 Participants	3 Participants	12 Participants	4 Participants	2 Participants	2 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Investigations	3 Participants	3 Participants	2 Participants	8 Participants	5 Participants	3 Participants	2 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Blood and lymphatic system disorders	2 Participants	4 Participants	2 Participants	7 Participants	3 Participants	3 Participants	3 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies General disorders and administration site conditions	2 Participants	3 Participants	1 Participants	9 Participants	5 Participants	2 Participants	1 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Metabolism and nutrition disorders	1 Participants	1 Participants	1 Participants	4 Participants	3 Participants	1 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Skin and subcutaneous tissue disorders	1 Participants	3 Participants	0 Participants	4 Participants	1 Participants	0 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Musculoskeletal and connective tissue disorders	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Respiratory, thoracic and mediastinal disorders	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Vascular disorders	0 Participants	2 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Cardiac disorders	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Injury, poisoning and procedural complications	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-related Adverse Events on Phase 2 and Sub Studies Infections and infestations	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=4 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=10 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=4 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 n=12 Participants Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 n=6 Participants Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 n=6 Participants Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) n=7 Participants Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Progression Free Survival (PFS) Time for Phase 2 and Sub Studies	54.0 days Interval 50.0 to Could not be calculated due to insufficient number of participants with events	56.0 days Interval 50.0 to 236.0	85.0 days Interval 58.0 to Could not be calculated due to insufficient number of participants with events	63.0 days Interval 44.0 to 97.0	87.0 days Interval 33.0 to 107.0	177.0 days Interval 62.0 to Could not be calculated due to insufficient number of participants with events	65.0 days Interval 23.0 to Could not be calculated due to insufficient number of participants with events

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=4 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=10 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=4 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 n=12 Participants Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 n=6 Participants Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 n=6 Participants Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) n=7 Participants Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Overall Survival (OS) Time for Phase 2 and Sub Studies	114.5 Days Interval 85.0 to Could not be calculated due to insufficient number of participants with events	346.5 Days Interval 76.0 to Could not be calculated due to insufficient number of participants with events	218.5 Days Interval 58.0 to Could not be calculated due to insufficient number of participants with events	261.0 Days Interval 121.0 to Could not be calculated due to insufficient number of participants with events	127.0 Days Interval 33.0 to Could not be calculated due to insufficient number of participants with events	177.0 Days Interval 62.0 to Could not be calculated due to insufficient number of participants with events	139.0 Days Interval 23.0 to Could not be calculated due to insufficient number of participants with events

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=1 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=1 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 n=1 Participants Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies	51 days	52 days	734 days	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 Min) Cohort 1 n=6 Participants Patients who received Tinostamustine at 60mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 Min) Cohort 2 n=7 Participants Patients who received Tinostamustine at 80mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 Min) Cohort 3 Patients who received Tinostamustine at 100mg/m2 (30min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 Min) Cohort 4 Patients who received Tinostamustine at 60mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 Min) Cohort 5 Patients who received Tinostamustine at 80mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 Min) Cohort 6 Patients who received Tinostamustine at 100mg/m2 (60min) on D1 and D15 of a 4-week cycle	Tinostamustine (EDO-S101) - Sub Study 2 (SS2) Subgroup treated with a dose of 80 mg/m2 over 80 minutes infusion time of EDO-S101
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 Interval 0.9 to 58.2	0 percentage of participants Interval 0.0 to 34.8	—	—	—	—	—
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 Interval 15.3 to 84.7	14.3 percentage of participants Interval 0.7 to 52.1	—	—	—	—	—

SECONDARY outcome

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.

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.