A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma

Phase 2TerminatedNCT04996004

Pfizer76 enrolled

Overview

The purpose of this study is to learn about the safety and effects of the study medicine (called Ontorpacept or TTI-621) when given alone and when given in combination with doxorubicin for people with leiomyosarcoma. Leiomyosarcoma is a tumor of the smooth muscles. This study is seeking participants who have: * leiomyosarcoma that is advanced or has spread to other parts of the body (metastatic) * not received prior treatment with anthracyclines (a drug commonly used in patients with some kinds of cancer, including leiomyosarcoma) * not received more than one prior treatment for their leiomyosarcoma During the first 18 weeks of this study, participants will receive doxorubicin by IV infusion (given directly into a vein) at the study clinic every 3 weeks for a total of 6 doses. Participants will also receive Ontorpacept (TTI-621) by IV infusion at the study clinic on the same day as doxorubicin and again one week later for the first 18 weeks. After the first 18 weeks, participants will stop receiving doxorubicin but will continue receiving Ontorpacept (TTI-621) as IV infusion every 14 days at the study clinic. They will keep receiving Ontorpacept (TTI-621) until their cancer is no longer responding to treatment. We will examine the experiences of participants receiving Ontorpacept (TTI-621) in combination with doxorubicin in the first 18 weeks and then Ontorpacept (TTI-621) by itself after the doxorubicin is stopped. This will help us determine if the study medicine Ontorpacept (TTI-621) given with doxorubicin and then by itself is safe and effective. Participants will be involved in the study for approximately one year, depending on how their cancer responds to the study treatment. They will have study visits about 12 times in the first 18 weeks (when the study medicine Ontorpacept is given with doxorubicin) and then every two weeks after the doxorubicin is stopped and the study medicine Ontorpacept (TTI-621) is given by itself.

This trial will be conducted in 2 phases: Phase I (dose escalation of Ontorpacept in combination with fixed-dose doxorubicin) and Phase II (dose expansion of Ontorpacept in combination with fixed-dose doxorubicin). Phase I will enroll patients with soft-tissue sarcomas including leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma or epithelioid sarcoma to evaluate escalating doses of Ontorpacept (TTI-621) administered in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy. Phase II will enroll patients with high-grade leiomyosarcoma and will evaluate two dose levels of Ontorpacept (TTI-621) in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy. .

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1. 2. Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation. 1. In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma 2. In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma. 3. Objective evidence of disease progression unless disease is newly-diagnosed. 4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts). 5. Adequate organ and hematologic function. 6. No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel. 7. Anthracycline-naïve. 8. Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment. 9. All adverse events from prior treatment must be NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline. 10. Radiotherapy, including palliative radiotherapy, completed at least two weeks prior to treatment; palliative radiation to non-target lesions while on study is allowed. Key Exclusion Criteria: 1. History of acute coronary syndromes. 2. History of or current Class II, III, or IV heart failure. 3. History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis. 4. Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract. 5. History of severe hypersensitivity reactions to antibodies. 6. Systemic steroid therapy. 7. History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs. 8. Prior organ transplantation including allogenic or autologous stem cell transplantation 9. Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.

Locations (23)

Sarcoma Oncology Research Center

Santa Monica, California, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

University of Michigan

Ann Arbor, Michigan, United States

MSK Basking Ridge.

Basking Ridge, New Jersey, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

MSK Monmouth

Middletown, New Jersey, United States

MSK Bergen

Montvale, New Jersey, United States

MSK Commack.

Commack, New York, United States

...and 13 more locations

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I

An adverse event (AE) was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A serious adverse event (SAE) was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure.

Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)

Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I

Blood pressure included diastolic blood pressure (DBP) and systolic blood pressure (SBP). Mean change from baseline to 30 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 1

Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 1

Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 30 minutes post dose on Day 8 of Cycle 1

Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 60 minutes post dose on Day 8 of Cycle 1

Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 2

Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 2

Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 3

Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I

Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 3

Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I

Blood pressure included DBP and SBP. Mean change from baseline to safety follow up visit were reported in this outcome measure. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, Safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)

Mean Change From Baseline in Body Weight at C3D1: Phase I

Body weight was measured in kilograms (kg). Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, Day 1 of Cycle 3

Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I

Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, Day 1 of Cycle 5

Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I

Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Time frame: Baseline, Day 1 of Cycle 7

Mean Change From Baseline in Body Weight at Safety Follow up: Phase I

Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).

Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I

Standard 12- lead ECGs, average of triplicate assessments were obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (millisecond \[msec\]): value greater than or equal to (\>=) 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by Bazzette's formula (QTcB) interval and QT correct by Frederica formula (QTcF) interval (msec): value greater than (\>) 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported.

Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I

The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, white blood cells (WBC), neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, Red blood cells (RBC), absolute reticulocytes, reticulocytes percentage (%), Mean corpuscular hemoglobin (MCH), Mean corpuscular volume (MCV) and Red cell distribution width (RDW). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.

Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)

Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I

The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, indirect bilirubin, uric acid, calcium, magnesium, lactate dehydrogenase (LDH). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.

Number of Participants With Dose Modifications: Phase I

Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed.

Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin)

Number of Participants With Treatment Discontinuations: Phase I

Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure.

Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin)

Objective Response Rate (ORR): Phase I and Phase II

ORR: percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator's assessment per response evaluation criteria in solid tumours RECIST version (v)1.1. BOR: best response recorded from start of treatment until disease progression (PD). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than(\< )10 mm. PR: at least 30 percent (%) decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study.

Time frame: From the start of study treatment until disease progression (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Secondary Outcomes

Number of Participants With TEAEs and Serious TEAEs: Phase II

An AE was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A SAE was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure.

Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)

Mean Change From Baseline in Blood Pressure: Phase II

Time frame: Baseline, 30 and 60min post dose of C1D1,C1D8,C2D1,C3D1 and safety follow up 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure of Phase II:88 weeks;maximum follow up:92 weeks)

Mean Change From Baseline in Body Weight: Phase II

Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1)

Time frame: Baseline, Day 1 of Cycle 3, 5, 7 and safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest [maximum treatment exposure for Phase II was 88 weeks; maximum follow up to 92 weeks])

Number of Participants With Overall ECG Abnormalities: Phase II

Standard 12- lead ECGs, average of triplicate assessments was obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (msec): \>= 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by QTcB interval and QT correct by QTcF interval (msec): value \> 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported.

Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II

The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, WBC, neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, RBC, absolute reticulocytes, reticulocytes %, MCH, MCV and RDW. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.

Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)

Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II

The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin, indirect bilirubin, uric acid, calcium, magnesium and LDH. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.

Progression Free Survival (PFS): Phase I and Phase II

PFS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever occurred first. PD was defined at least 20% increase in sum of longest diameter (LD) of target lesion, taking reference of smallest sum on study. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier. Kaplan-Meier method was used for analysis.

Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Overall Survival (OS): Phase I and Phase II

OS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause. Participants last known to be alive were censored at their last known alive date. Kaplan-Meier method was used for analysis.

Time frame: From the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Disease Control Rate (DCR): Phase I and Phase II

DCR was defined as the percentage of participants who have achieved CR, PR, or SD lasting at least 4 weeks as per RECIST v1.1 CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study.

Time frame: From the first dose of study treatment until PD or death, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Duration of Response (DOR): Phase I and Phase II

DOR was defined as time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response. DOR was calculated for participants who achieved CR or PR. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier.

Time frame: Time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Duration of Disease Control (DDC): Phase I and Phase II

DDC: participants who achieved BOR of SD, as time from first ontorpacept infusion (Day1 of Cycle1) to date of documented PD/death of any cause. Calculated for participants who achieved CR,PR/SD lasting at least 4weeks. CR:disappearance of all target lesion. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR:at least 30%decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD:at least 20% increase in sum of LD of target lesion, taking reference of smallest sum on study. Participants without PD/death/with an event after 2/more missing/inadequate disease assessment/with event after start date of alternate anticancer therapy were censored at last response assessment date/last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier.

Time frame: Time from first ontorpacept infusion (Day 1 of Cycle 1) to date of documented progression/death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Time to Progression (TTP): Phase I and Phase II

TTP was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever is first; provided death was not considered as an event. PD: at least 20% increase in sum of longest diameter of target lesion, taking reference of smallest sum on study. Participants without PD or death or with an event after 2 or more missing or inadequate disease assessment or with event after start date of alternate anticancer therapy were censored at last response assessment date or last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier.

Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever is first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Time to New Metastases: Phase I and Phase II

Time to new metastasis was defined as the time from the ontorpacept infusion (Day 1 of Cycle 1) to a new lesion appearance. Participants without new lesion or participants with new metastases after 2 or more missing/inadequate disease assessment or participants with new metastases after the start date of alternate anti-cancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy whichever was earlier.

Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) until the appearance of new lesion or death or censoring date, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)

Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II

ECOG performance were classified as 5 grades: 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2: ambulatory and capable of all selfcare but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited selfcare, confined to bed or chair more than 50% of waking hours and 4: completely disabled, cannot carry on selfcare and totally confined to bed or chair. Higher score indicated lower health status. Worsening of ECOG was defined as a worsening from baseline (i.e., increase) in the ECOG assessment level and was recorded in two consecutive assessments.

Time frame: From Baseline up to 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred first (maximum exposure upto 74.1 and 88 weeks; maximum follow up to approx. 78.1 and 92 weeks for Phase I and II respectively)

Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II

QOL was assessed with European organisation for research and treatment of cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) tool. The EORTC QLQ-C30 is self-administered, self-reported general cancer-specific questionnaire consisting of 30 items covered by one of 3 dimensions: global health status (2 items): functional scales(15 total items addressing either physical, emotional, cognitive/social functioning) and symptom scales(13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea/financial impact). Higher score indicated better overall QoL. Worsening of Global Health Status /QoL assessments was defined as at least a 10-point decrease from baseline in the standardized score (linear transformation) of Global Health Status/QoL.

A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma

Overview

Conditions

Interventions

Eligibility

Locations (23)

Outcomes

Primary Outcomes

Secondary Outcomes