A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma (TTI-621-03)

A Phase I/II Study of TTI-621 in Combination With Doxorubicin in Patients With Unresectable or Metastatic High-Grade Leiomyosarcoma

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.

Study Overview

• Status: Terminated
• Conditions: Leiomyosarcoma
• Intervention / Treatment: Drug: Doxorubicin; Drug: Ontorpacept (TTI-621)

Detailed Description

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.

.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSK Basking Ridge.
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Middletown, New Jersey, United States, 07748
      • MSK Monmouth
    • Montvale, New Jersey, United States, 07645
      • MSK Bergen
  • New York
    • Commack, New York, United States, 11725
      • MSK Commack.
    • Harrison, New York, United States, 10604
      • MSK Westchester
    • Long Island City, New York, United States, 11101
      • Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - Main Campus
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center 53rd street.
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center 53rd street.
    • Uniondale, New York, United States, 11553
      • MSK Nassau
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University - Center for Health and Healing 2(CHH2)
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University - Center for Health and Healing 1 (CHH1)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center

Participation Criteria

Eligibility Criteria

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

Description

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.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Ontorpacept+doxorubicin); In the dose escalation portion of the study, participants with specific subsets of soft tissue sarcomas who have not received more than one prior line of therapy and have not received an anthracycline in any setting will be enrolled in three escalating dose cohorts to characterize the safety and tolerability of Ontorpacept (TTI-621) when administered in combination with doxorubicin for up to six cycles and followed by Ontorpacept (TTI-621) monotherapy	Drug: Doxorubicin; 75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.; Other Names: Adriamycin; Drug: Ontorpacept (TTI-621); Ontorpacept (TTI-621) will be administered by intravenous infusion.; Other Names: Ontorpacept / SIRPα-IgG1 Fc
Experimental: Dose Expansion Dose Level A (Cohort A); Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level A) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.	Drug: Doxorubicin; 75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.; Other Names: Adriamycin; Drug: Ontorpacept (TTI-621); Ontorpacept (TTI-621) will be administered by intravenous infusion.; Other Names: Ontorpacept / SIRPα-IgG1 Fc
Experimental: Dose Expansion Dose Level B (Cohort B); Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level B) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.	Drug: Doxorubicin; 75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.; Other Names: Adriamycin; Drug: Ontorpacept (TTI-621); Ontorpacept (TTI-621) will be administered by intravenous infusion.; Other Names: Ontorpacept / SIRPα-IgG1 Fc
Experimental: Dose Expansion Dose Level C (Cohort C); Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level C) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.	Drug: Doxorubicin; 75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.; Other Names: Adriamycin; Drug: Ontorpacept (TTI-621); Ontorpacept (TTI-621) will be administered by intravenous infusion.; Other Names: Ontorpacept / SIRPα-IgG1 Fc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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).	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).	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).	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).	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).	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).	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).	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).	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).	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).	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).	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).	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)
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.	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)
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.	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.	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 Dose Modifications: Phase I	Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed.	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.	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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).	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)	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.	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)
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.	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.	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 Dose Modifications: Phase II	Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed.	During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin)
Number of Participants With Treatment Discontinuations: Phase II	Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure.	During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin)
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 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.	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.	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 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 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 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 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.	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.	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)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): December 7, 2023
• Study Completion (Actual): December 7, 2023

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Leiomyosarcoma; Pleomorphic sarcoma; Myxofibrosarcoma; Liposarcoma; Angiosarcoma; Epithelioid sarcoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Leiomyosarcoma; Antibiotics, Antineoplastic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Doxorubicin
• Other Study ID Numbers: TTI-621-03; C4961003 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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