What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as chemotherapy, hormone therapy, targeted therapy, and immunotherapy, have various side effects. Chemotherapy can cause nausea, vomiting, hair loss, fatigue, and increased risk of infections. Hormone therapies like tamoxifen may lead to hot flashes, vaginal dryness, and an increased risk of blood clots. Targeted therapies, such as trastuzumab, can cause fever, chills, nausea, and cardiac dysfunction. Immunotherapies, including CAR T-cell therapies like LYL797, may result in cytokine release syndrome, neurological toxicities, and increased risk of infections. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

As of now, there are no FDA-approved ROR1-targeted CAR T-cell therapies specifically for breast cancer. However, CAR T-cell therapies have been approved for other types of cancers, such as B-cell lymphomas and acute lymphoblastic leukemia. For breast cancer, FDA-approved treatments include hormone therapies (e.g., tamoxifen, aromatase inhibitors), HER2-targeted therapies (e.g., trastuzumab, pertuzumab), and CDK4/6 inhibitors (e.g., palbociclib). These treatments target specific pathways and receptors involved in breast cancer growth and progression. The investigational LYL797 therapy represents a novel approach by targeting the ROR1 protein, which could offer new hope for patients with relapsed or refractory triple-negative breast cancer.

What other types of research exist?

Promising novel alternatives to LYL797 for breast cancer patients in 2024 include: 1) Pembrolizumab plus palbociclib, which is being investigated for HR+ metastatic breast cancer, showing potential in enhancing immune response and inhibiting cell cycle progression. 2) Selpercatinib, a selective RET inhibitor, which has shown efficacy in RET-altered cancers and could be relevant for specific genetic profiles in breast cancer. 3) Acalabrutinib, a BTK inhibitor, which is being explored for its potential in various B-cell malignancies and may offer benefits in certain breast cancer subtypes. These alternatives represent different mechanisms of action and are in various stages of clinical evaluation.

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CAR T-cell Therapy

LYL797 for Breast and Lung Cancer

Phase 1

Recruiting

Research Sponsored by Lyell Immunopharma, Inc.

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

≥ 18 years of age at time of informed consent

Must not have

Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors

Prior treatment with any adoptive T-cell therapy or anti-ROR1 therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment called LYL797, which uses modified immune cells to target and kill hard-to-treat breast and lung cancer cells. The study aims to find a safe dose and see how well it works in patients whose cancers have not responded to other treatments.

Who is the study for?

Adults with advanced, ROR1+ triple negative breast cancer or non-small cell lung cancer that's come back or hasn't responded to treatment. They must be in good physical condition, have proper organ and marrow function, not be pregnant, and agree to use effective birth control. People can't join if they've had certain other treatments like adoptive T-cell therapy, have untreated brain metastasis, active infections including HIV/HBV/HCV/TB, serious heart issues, uncontrolled fluid around lungs/heart or are on immunosuppressants.

What is being tested?

LYL797 is being tested for safety and the right dose in patients with specific types of breast and lung cancers. The first part finds a safe dose by starting low then increasing it for new groups of patients (dose escalation). Once found, the second part tests this dose in more patients (dose expansion).

What are the potential side effects?

Possible side effects aren't detailed but may include symptoms typical of CAR T-cell therapies such as fever, fatigue, immune reactions affecting different organs (cytokine release syndrome), neurological events among others.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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I am 18 years old or older.

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I am of childbearing age and my pregnancy test was negative.

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My cancer is triple-negative breast cancer or non-small cell lung cancer, cannot be surgically removed, and tests positive for ROR1.

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I have at least two detectable cancer lesions.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am on long-term blood thinners like warfarin.

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I have not had T-cell or anti-ROR1 therapy before.

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I have had a solid organ transplant.

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I do not have an active infection.

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I have heart problems that affect my daily activities.

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I have fluid buildup around my lungs or heart that isn't managed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Determine recommended Phase 2 Dose (RP2D)

Evaluate incidence of dose-limiting toxicities (DLTs)

Evaluate incidence of treatment-emergent adverse events (TEAEs)

+1 more

Secondary study objectives

Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples

Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1

Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)

+5 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Experimental LYL797Experimental Treatment1 Intervention

ROR1-targeted CAR T cells

0 / 11Eligibility criteria met

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

ROR1-targeted CAR T-cell therapy, like the one studied in the LYL797 trial, involves engineering a patient's T-cells to express a chimeric antigen receptor (CAR) that specifically targets the ROR1 protein on cancer cells, leading to the destruction of these cells. This is particularly relevant for patients with triple-negative breast cancer (TNBC), which lacks hormone receptors and HER2 expression, making it less responsive to traditional hormone therapies and HER2-targeted treatments. Understanding the mechanisms of action of these therapies helps patients and doctors make informed decisions about treatment options, especially for aggressive and hard-to-treat forms of breast cancer like TNBC.

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