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

NCT04996004 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: TTI-621-03C4961003
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Leiomyosarcoma

Keywords

Leiomyosarcoma; Pleomorphic sarcoma; Myxofibrosarcoma; Liposarcoma; Angiosarcoma; Epithelioid sarcoma

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (17)

• Number of Participants With TEAEs and Serious TEAEs: Phase II

  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

  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, 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

  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

  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)

Study Arms (4)

Dose Escalation (Ontorpacept+doxorubicin)

EXPERIMENTAL

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: Ontorpacept (TTI-621); Drug: Doxorubicin

Dose Expansion Dose Level A (Cohort A)

EXPERIMENTAL

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: Ontorpacept (TTI-621); Drug: Doxorubicin

Dose Expansion Dose Level B (Cohort B)

EXPERIMENTAL

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: Ontorpacept (TTI-621); Drug: Doxorubicin

Dose Expansion Dose Level C (Cohort C)

EXPERIMENTAL

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: Ontorpacept (TTI-621); Drug: Doxorubicin

Interventions

Ontorpacept (TTI-621) DRUG

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Also known as: Ontorpacept / SIRPα-IgG1 Fc

Dose Escalation (Ontorpacept+doxorubicin); Dose Expansion Dose Level A (Cohort A); Dose Expansion Dose Level B (Cohort B); Dose Expansion Dose Level C (Cohort C)

Doxorubicin DRUG

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Also known as: Adriamycin

Dose Escalation (Ontorpacept+doxorubicin); Dose Expansion Dose Level A (Cohort A); Dose Expansion Dose Level B (Cohort B); Dose Expansion Dose Level C (Cohort C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1.
• Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation.
• In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma
• In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma.
• Objective evidence of disease progression unless disease is newly-diagnosed.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts).
• Adequate organ and hematologic function.
• No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel.
• Anthracycline-naïve.
• Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment.
• 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.
• Radiotherapy, including palliative radiotherapy, completed at least two weeks prior to treatment; palliative radiation to non-target lesions while on study is allowed.

You may not qualify if:

• History of acute coronary syndromes.
• History of or current Class II, III, or IV heart failure.
• History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis.
• Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract.
• History of severe hypersensitivity reactions to antibodies.
• Systemic steroid therapy.
• History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
• Prior organ transplantation including allogenic or autologous stem cell transplantation
• Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (23)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MSK Basking Ridge.

Basking Ridge, New Jersey, 07920, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MSK Monmouth

Middletown, New Jersey, 07748, United States

Location

MSK Bergen

Montvale, New Jersey, 07645, United States

Location

MSK Commack.

Commack, New York, 11725, United States

Location

MSK Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy

Long Island City, New York, 11101, United States

Location

Memorial Sloan Kettering Cancer Center 53rd street.

New York, New York, 10022, United States

Location

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center 53rd street.

New York, New York, 10065, United States

Location

MSK Nassau

Uniondale, New York, 11553, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Oregon Health and Science University - Center for Health and Healing 1 (CHH1)

Portland, Oregon, 97239, United States

Location

Oregon Health and Science University - Center for Health and Healing 2(CHH2)

Portland, Oregon, 97239, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

Related Links

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

MeSH Terms

Conditions

Leiomyosarcoma; Dermatofibrosarcoma; Liposarcoma; Hemangiosarcoma; Sarcoma

Interventions

TTI-621; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 9, 2021
• Study Start: June 22, 2021
• Primary Completion: December 7, 2023
• Study Completion: December 7, 2023
• Last Updated: December 11, 2024
• Results First Posted: December 11, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (23)