Study of the Safety, Pharmacokinetics and Efficacy of Tinostamustine in Patients With Advanced Solid Tumors. (EDO-S101)

A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of EDO-S101, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 60mg/m2 Administered During a 60 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 80mg/m2 Administered During a 80 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors.

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.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma; Small Cell Lung Cancer; Ovarian Cancer; Endometrial Cancer; Triple-negative Breast Cancer
• Intervention / Treatment: Drug: Tinostamustine 60mg/m2 over 30min; Drug: Tinostamustine 80mg/m2 over 30min; Drug: Tinostamustine 100mg/m2 over 30min; Drug: Tinostamustine 60mg/m2 over 60min; Drug: Tinostamustine 80mg/m2 over 60min; Drug: Tinostamustine 100mg/m2 over 60min; Drug: Tinostamustine 80mg/m2 over 80min

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario, ON
    • Hamilton, Ontario, ON, Canada, L8V 1C3
      • Juravinski Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University
  • Vancouver, BC
    • Vancouver, Vancouver, BC, Canada, V5Z 1M9
      • BC Cancer-Vancouver
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, MI 20141
    • Istituto Europeo di Oncologia
• Netherlands
  • Rotterdam, Netherlands, 3015
    • Erasmus MC Kanker Instituut
• Spain
  • Fuencarral-El Pardo
    • Madrid, Fuencarral-El Pardo, Spain, 28046
      • Hospital Universitario La Paz
  • Horta-Guinardó
    • Barcelona, Horta-Guinardó, Spain, 08035
      • Hospital Universitari Vall d'Hebron
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10016
      • New York University
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria Phase 1 and Phase 2 portions of Study:

To be eligible to participate in the trial, a patient cannot meet any of the following exclusion criteria:

1. Patients with primary central nervous system (CNS) cancer.
2. Patients with QTc interval (Fridericia's formula) >450 msec.
3. Patients who are on treatment with drugs known to prolong the QT/QTc interval.
4. Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder).
5. Any serious medical condition that interferes with adherence to trial procedures.
6. Prior history of solid tumor malignancy diagnosed within the last three (3) years of study enrollment excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment)
7. Pregnant or breast feeding females.
8. New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias not adequately controlled, or other significant co-morbidities [e.g. active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C].
9. Use of other investigational agents within 28 days prior to the first dose of study drug, provided the patient has recovered from any related toxicities ≥Grade 1.
10. Steroid treatment within seven (7) days prior to trial treatment. Patients that require intermittent use of bronchodilators, topical steroids or local steroid injections will not be excluded from the study. Patients who have been stabilized to 10 mg Prednisolone orally (PO) once daily (QD) (or equivalent), daily (or less) at least seven (7) days prior to IMP administration are allowed.

Phase 2:

Patients must meet the cohort-specific inclusion/exclusion criteria in addition to the general inclusion/exclusion criteria for Phase 1 and Phase 2 study listed above.

Cohort 1: Relapsed/Refractory small cell lung cancer (SCLC)

1. Histologically or cytologically confirmed limited or extensive disease stage of SCLC.
2. Must have received at least 1 line of prior combination chemotherapy or biological 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.
3. At least 28 days should have elapsed since prior treatment as long as the patient has recovered from any related toxicities to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
4. Prior radiotherapy is acceptable provided the patient has recovered from any radiotherapy related acute toxicities.
5. The disease should be progressing during or relapsing after the previous treatment.
6. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.

Cohort 2: Relapsed/Refractory Soft Tissue Sarcoma (STS)

1. Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy excluding: neuroblastoma, GIST, embryonal rhabdomyosarcoma, Kaposi sarcoma, chondrosarcoma, osteosarcoma or Ewing's sarcoma.
2. Must have received at least one prior line prior line chemotherapy or biological therapy regimen 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. At least twenty-eight (28) days should have elapsed since prior chemotherapy, as long as the patient recovered from any related toxicities to ≤ Grade 1 (or ≤Grade 2 for any symptomatic neuropathy or endocrinopathies).
3. The disease should be progressing during or relapsing after the previous treatment.
4. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.

Cohort 3: Relapsed/Refractory Triple Negative Breast Cancer (TNBC)

1. Histologically or cytologically confirmed locally advanced or metastatic Triple Negative Breast Cancer. Proven human epidermal growth factor receptor 2 (HER2) negative by immunohistochemistry (INH) or in situ hybridization (ISH) per per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines.
2. Must have received at least one (1) line of chemotherapy or biological therapy and no other standard therapy with proven clinical benefit was available or recommended based on the Investigator's individual risk-benefit assessment for the subject.
3. At least three (3) weeks should have elapsed since prior chemotherapy as long as the subject recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
4. Prior radiotherapy was acceptable provided it was administered at least four (4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this study and the subject recovered from any radiotherapy related acute toxicities.
5. The disease had to be progressing during or relapsing after the previous treatment.
6. Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion.

Cohort 4: Patient Population: Relapsed/Refractory Ovarian Cancer (OC)

1. Histologically or cytologically confirmed advanced ovarian cancer: epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer (excluding borderline ovarian cancer, MMMT) of high grade serous histology, or high grade endometrioid cancer, that is resistant or refractory to platinum 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. Clear cell carcinomas are excluded. Patients with primary platinum refractory disease (failure to respond to initial platinum treatment or relapse within four (4) weeks) and patients with primary platinum resistant disease (progression within six (6) months of completing first line platinum-based therapy) are excluded from the study.
2. At least twenty eight (28) days should have elapsed since prior chemotherapy as long as the patient recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
3. The disease should be progressing during or relapsing after the previous treatment.
4. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.

Cohort 5: Relapsed/Refractory Endometrial Cancer (EC)

1. Histologically or cytologically confirmed locally advanced or metastatic endometrial cancer (excluding leiomyosarcoma and carcinosarcoma)
2. Must have received at least one (1) line of chemotherapy 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. At least three (3) weeks should have elapsed since prior chemotherapy or 5 half-lives, whichever is shorter, as long as the patient recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
3. Prior radiotherapy is acceptable provided it was administered at least four(4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this trial and recovered from any radiotherapy related acute toxicities.
4. The disease should be progressing/relapsed during or after the previous treatment.
5. Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort	Drug: Tinostamustine 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.; Other Names: EDO-S101.
Experimental: Tinostamustine (EDO-S101) - Sub study 1 (SS1)	Drug: Tinostamustine 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.; Other Names: EDO-S101
Experimental: Tinostamustine (EDO-S101) - Sub study 2 (SS2)	Drug: Tinostamustine 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.; Other Names: EDO-S101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.
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.	From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days.
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.	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).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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.	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.
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.	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.
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.	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.
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.	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)
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.	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).
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.
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.
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.

Collaborators and Investigators

• Sponsor: Mundipharma Research Limited
• Investigators: Principal Investigator: Shivaani Kummar, MD, Oregon Health and Science University; Principal Investigator: Ana Oaknin, MD, Head of Gynaecologic Cancer Program, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): March 29, 2023

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Advanced; Metastatic; Triple Negative; Solid Tumor; Relapsed/Refractory; Fallopian tube cancer; Small Cell Lung Cancer (SCLC); Peritoneal cancer; Gastrointestinal stromal tumors (GIST); Epithelial cancer; Phase 1 (P1); Ovarian Cancer (OC); Soft Tissue Sarcoma (STS); 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)
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Sarcoma; Ovarian Neoplasms; Endometrial Neoplasms; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms
• Other Study ID Numbers: EDO-S101-1002; 2020-004246-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Relevant patient listing data of de-identified patients may be reviewed
• IPD Sharing Time Frame: Available on request through Enquiries@napp.co.uk
• IPD Sharing Access Criteria: Available on request through Enquiries@napp.co.uk
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No