What side effects are associated with this type of intervention?

Common treatments for leiomyosarcoma, such as doxorubicin, often cause side effects like nausea, vomiting, hair loss, myelosuppression, and cardiotoxicity. Ontorpacept (TTI-621), a CD47-SIRPα pathway inhibitor under investigation, may cause infusion-related reactions, fatigue, and immune-related adverse events. Patients should discuss these potential side effects with their doctor to make informed treatment decisions.

What prior FDA approvals exist?

The provided context does not mention specific FDA approvals for treatments targeting the CD47-SIRPα pathway in leiomyosarcoma. However, it does reference the study of Ontorpacept (TTI-621) in combination with doxorubicin for advanced or metastatic leiomyosarcoma. Generally, treatments for leiomyosarcoma include chemotherapy agents like doxorubicin, and other targeted therapies are being explored in clinical trials.

What other types of research exist?

Promising novel alternatives to Ontorpacept (TTI-621) for Leiomyosarcoma patients include: 1) IMC-A12 (anti-IGF-1 receptor antibody) in combination with rapamycin, which has shown significant antitumor activity in preclinical models. 2) Dual PI3K/mTOR inhibitors like BGT226, which have demonstrated effectiveness in reducing tumor proliferation in lymphoma models. 3) Everolimus, an mTORC1 inhibitor, which has been effective in various tumor models and could be considered for combination therapies.

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Anti-tumor antibiotic

Ontorpacept + Doxorubicin for Leiomyosarcoma (TTI-621-03 Trial)

Phase 2

Waitlist Available

Research Sponsored by Trillium Therapeutics Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from initiation of treatment until discontinuation from study (up to approximately 29 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new medicine called Ontorpacept, alone and with doxorubicin, in people with advanced leiomyosarcoma. Ontorpacept helps the immune system fight cancer, and doxorubicin kills cancer cells. The study aims to see if this combination is safe and effective.

Who is the study for?

This trial is for people with advanced leiomyosarcoma, a type of muscle tumor, who haven't been treated with anthracyclines and have had at most one other treatment. Participants should be in good overall health with no severe allergies to antibodies or history of certain autoimmune diseases or organ transplants.

What is being tested?

The study tests Ontorpacept (TTI-621) alone and combined with Doxorubicin in treating leiomyosarcoma. Initially, both drugs are given by IV every three weeks for 18 weeks; afterwards, only Ontorpacept is continued biweekly until it's not effective anymore.

What are the potential side effects?

Possible side effects include reactions related to the immune system due to antibody therapy, potential heart issues from Doxorubicin, and general risks like fatigue and nausea associated with chemotherapy treatments.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from initiation of treatment until discontinuation from study (up to approximately 29 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from initiation of treatment until discontinuation from study (up to approximately 29 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from initiation of treatment until discontinuation from study (up to approximately 29 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean and changes from baseline in blood pressure

Percentage of patients with objective response

Secondary study objectives

Categorical summary of ECG parameters

Disease control rate (DCR)

Duration of disease control (DDC)

+12 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose Expansion Dose Level C (Cohort C)Experimental Treatment2 Interventions

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.

Group II: Dose Expansion Dose Level B (Cohort B)Experimental Treatment2 Interventions

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.

Group III: Dose Expansion Dose Level A (Cohort A)Experimental Treatment2 Interventions

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.

Group IV: Dose Escalation (Ontorpacept+doxorubicin)Experimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Doxorubicin

2012

Completed Phase 3

~8030

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Leiomyosarcoma include doxorubicin and emerging therapies like Ontorpacept (TTI-621). Doxorubicin works by intercalating DNA strands, preventing cancer cell replication and inducing apoptosis. Ontorpacept (TTI-621) is a CD47-SIRPα pathway inhibitor that blocks the 'don't eat me' signal used by cancer cells to evade the immune system, thereby promoting their destruction by macrophages. These mechanisms are significant for Leiomyosarcoma patients as they offer a dual approach: traditional chemotherapy to directly kill cancer cells and immune-modulating therapy to enhance the body's ability to target and destroy cancer cells.

Deciphering the molecular mechanism of tetrandrine in inhibiting hepatocellular carcinoma and increasing sorafenib sensitivity by combining network pharmacology and experimental evaluation.Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-cell Acute Lymphoblastic Leukemia.Rapamycin targeting mTOR and hedgehog signaling pathways blocks human rhabdomyosarcoma growth in xenograft murine model.