Trial Outcomes & Findings for A Study of TP-0184 to Treat Anemia in Adults With IPSS-R Low or Intermediate Risk MDS (NCT NCT04623996)

Results Overview

DLTs are defined as follows: Any Gr 3 or greater nonhematologic toxicity; New onset cardiac failure or worsening symptomatic cardiac failure; Echocardiogram (ECHO) or multigated acquisition (MUGA) reduction of ejection fraction (EF) \> 10%; Any Gr 4 neutropenia; Any Gr 3 thrombocytopenia associated with clinically significant bleeding, or Gr 4 thrombocytopenia in the absence of myelodysplasia-related marrow failure or transformation to acute leukemia; All other hematologic toxicity Grade 3 or higher other than defined above for ANC or platelets

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Cycle 1 (28 days)

Results posted on

2023-11-09

Participant Flow

Due to limitations imposed by the COVID pandemic and the competitive landscape for myelodysplastic syndrome, this study was unable to enroll a sufficient patient population. The decision was made to terminate the study early and discontinue further development of the TP-0184 program. The 2 patients enrolled into phase 1 of the study withdrew their consent to participate on 30 March 2021 and 27 April 2021; no further patients were enrolled.

Participants who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.

Participant milestones

Participant milestones
Measure	Phase 1: Single Arm TP-0184 Participants who were enrolled to phase 1 received TP-0184, with starting dose of 20mg, administered orally, once daily, following an overnight fast of at least 6 hours.	Phase 2: Single Arm TP-0184 Participants who were enrolled to phase 2 would receive the recommended phase 2 dose (RP2D) as determined in phase 1.
Overall Study STARTED	2	0
Overall Study COMPLETED	2	0
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of TP-0184 to Treat Anemia in Adults With IPSS-R Low or Intermediate Risk MDS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: Single Arm TP-0184 n=2 Participants Participants who were enrolled to phase 1 received TP-0184, with starting dose of 20mg, administered orally, once daily, following an overnight fast of at least 6 hours.	Phase 2: Single Arm TP-0184 Participants who were enrolled to phase 2 would receive the recommended phase 2 dose (RP2D) as determined in phase 1.	Total n=2 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Age, Continuous	63 years n=5 Participants	—	63 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	—	2 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned.

DLTs are defined as follows: Any Gr 3 or greater nonhematologic toxicity; New onset cardiac failure or worsening symptomatic cardiac failure; Echocardiogram (ECHO) or multigated acquisition (MUGA) reduction of ejection fraction (EF) \> 10%; Any Gr 4 neutropenia; Any Gr 3 thrombocytopenia associated with clinically significant bleeding, or Gr 4 thrombocytopenia in the absence of myelodysplasia-related marrow failure or transformation to acute leukemia; All other hematologic toxicity Grade 3 or higher other than defined above for ANC or platelets

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: The time from the date of first treatment, while the patient is taking TP-0184, and for 30 days after stopping therapy, an average of 4 months.

Assessment of safety of TP-0184 administered in participants by reporting of adverse events and serious adverse events

Outcome measures

Outcome measures
Measure	Phase 1: Single Arm TP-0184 n=2 Participants Participants who were enrolled to phase 1 received TP-0184, with starting dose of 20mg, administered orally, once daily, following an overnight fast of at least 6 hours.	Phase 2: Single Arm TP-0184 Participants who were enrolled to phase 2 would receive the recommended phase 2 dose (RP2D) as determined in phase 1.
Phase 1: Number of Participants With Adverse Events and Serious Adverse Events	2 Participants	—

PRIMARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Response rate based on composite response criteria: Hemoglobin increase greater than or equal to 1.5 g/dL, maintained for a consecutive period of 8 weeks with no transfusions; OR reduction in units of greater than or equal to 4 RBC transfusions / 8 weeks (consecutive) compared with the pretreatment transfusion number in previous 8 weeks; OR patients who are RBC transfusion-free over any consecutive 8-week (56-day) period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned.

Response rate based on composite response criteria: Hemoglobin increase greater than or equal to 1.5 g/dL, maintained for a consecutive period of 8 weeks with no transfusions; OR reduction in units of greater than or equal to 4 RBC transfusions / 8 weeks (consecutive) compared with the pretreatment transfusion number in previous 8 weeks; OR patients who are RBC transfusion-free over any consecutive 8-week (56-day) period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 84 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Response rate based on composite response criteria: Hemoglobin increase greater than or equal to 1.5 g/dL, maintained for a consecutive period of 12 weeks with no transfusions; OR reduction in units of greater than or equal to 4 RBC transfusions / 12 weeks (consecutive) compared with the pretreatment transfusion number in previous 12 weeks; OR patients who are RBC transfusion-free over any consecutive 12-week (84-day) period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Time from first dose of TP-0184 to the first onset of a transfusion-free period for consecutive 8 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Duration of hemoglobin increase greater or equal to 1.5 g/dL maintained for a consecutive period of \> 8 weeks with no transfusions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Duration of reduction in units of greater or equal to 4 RBC transfusions / 8 weeks (consecutive)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Duration of RBC transfusion-free period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from the date of first treatment, while the patient is taking TP-0184, and for 30 days after stopping therapy, an average of 4 months.

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Assessment of cardiac safety of TP-0184 administered in participants by reporting of cardiac symptoms including congestive heart failure (CHF). Assessment of CHF will be based based on NYHA criteria, 12-Lead ECG abnormalities, quantification of cardiac iron by MRI, ECHO or MUGA scans, and peripheral blood cardiac markers

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Proportion of patients progressing to AML

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of TP-0184 until the time of death due to any cause, up to 4 months off treatment.

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

The effect of TP-0184 on the overall survival

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Phase 1: Blood samples drawn on days 1, 2, 4, 8, 15, and 22 of the first study cycle; days 1, 8, 15, and 16 of the 2nd cycle. Phase 2: Blood samples drawn on Cycle 1, day 22; cycle 2, days 1, 8 and 15; cycle 3, day 1.

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned.

To determine the maximum concentration of TP-0184 and the area under the plasma concentration vs. time curve of TP-0184

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients enrolled into phase 2.

Proportion of patients achieving hematologic improvement in neutrophil count (HI-N) over any consecutive 8-week (56-day) period and / or decrease in neutrophil count

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 56 days

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Proportion of patients achieving hematologic improvement in platelets (HI-P) over any consecutive 8-week (56-day) period and / or decrease in platelet count

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from the date of first treatment, while the patient is taking TP-0184, and for 30 days after stopping therapy, up to 6 months.

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients enrolled into phase 2.

Assessment of safety and tolerability of TP-0184 administered in participants by reporting of AEs and SAEs

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 of Week 4 and Cycle 2 Day 1 of each Week 5, 6, 7, and 9

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

Characterize TP-0184 plasma trough concentration data at various timepoints.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of TP-0184 up to 4 months or study closure

Population: Sponsor's decision to terminate further development of the TP-0184 program. Data collection and analysis were therefore not conducted as planned. No patients were enrolled into phase 2.

The BFI measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours

Outcome measures

Outcome data not reported

Adverse Events

Phase 1: Single Arm TP-0184

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1: Single Arm TP-0184 n=2 participants at risk Participants who were enrolled to phase 1 received TP-0184, with starting dose of 20mg, administered orally, once daily, following an overnight fast of at least 6 hours.
Injury, poisoning and procedural complications overdose	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.

Other adverse events

Other adverse events
Measure	Phase 1: Single Arm TP-0184 n=2 participants at risk Participants who were enrolled to phase 1 received TP-0184, with starting dose of 20mg, administered orally, once daily, following an overnight fast of at least 6 hours.
Gastrointestinal disorders nausea	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Gastrointestinal disorders diarrhoea	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
General disorders fatigue	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Nervous system disorders headache	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Eye disorders vision blurred	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Gastrointestinal disorders abdominal pain	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Gastrointestinal disorders dyspepsia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Nervous system disorders ageusia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Musculoskeletal and connective tissue disorders arthralgia	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Nervous system disorders anosmia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
General disorders chills	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Metabolism and nutrition disorders decreased appetite	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Investigations SARS-CoV-2 test positive	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Eye disorders dry eye	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Renal and urinary disorders dysuria	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Infections and infestations Klebsiella infection	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Musculoskeletal and connective tissue disorders pain in extremity	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.
Renal and urinary disorders pollakiuria	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death or withdrawal of consent, up to 4 months off treatment. Sponsor's decision to terminate further development of the TP-0184 program. No patients were enrolled into phase 2.

Additional Information

Tegan Nguyen

Sumitomo Pharma Oncology

Phone: 617-674-8745

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60