LYL797 for Breast and Lung Cancer

No longer recruiting at 21 trial locations

Overseen By Jackie Walling, MBChB, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lyell Immunopharma, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Organ transplant, Brain metastasis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment called LYL797, a type of CAR T-cell therapy targeting the protein ROR1. It is intended for patients with specific cancers, including triple-negative breast cancer, non-small cell lung cancer, ovarian cancer, and endometrial cancer, particularly if these cancers have returned or resisted other treatments. The study aims to determine a safe dose of LYL797 and evaluate its effectiveness in more patients. Suitable candidates are those whose cancer expresses the ROR1 protein and who have not succeeded with other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking systemic corticosteroids or other immunosuppressive medications at least 14 days before a specific procedure called leukapheresis. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that LYL797 is likely to be safe for humans?

Previous studies have tested LYL797, a therapy targeting cancer cells, for safety. Research shows it is generally well-tolerated by patients. Some studies have found that LYL797 works better at higher doses, suggesting greater effectiveness with larger amounts. In these studies, 60% of patients experienced positive effects from the treatment.

Although specific side effects are not detailed in the available data, LYL797's status in a Phase 1 trial indicates ongoing safety monitoring. Phase 1 trials aim to determine safe dosage levels and identify any side effects. If the treatment were unsafe, it would not have reached this stage. However, as with all early-stage treatments, the full safety profile is still being developed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LYL797 because it represents a new approach to treating breast and lung cancer. Unlike traditional treatments like chemotherapy and radiation that target rapidly dividing cells, LYL797 uses ROR1-targeted CAR T cells. This means it harnesses the body's own immune system to specifically hunt down and destroy cancer cells, potentially reducing harm to healthy cells and improving effectiveness. This targeted action could offer patients a more precise treatment with potentially fewer side effects.

What evidence suggests that LYL797 might be an effective treatment for breast and lung cancer?

Research has shown that LYL797, the investigational treatment in this trial, represents a new type of treatment called CAR T-cell therapy with potential for treating certain cancers. In studies, 60% of patients experienced a positive effect from LYL797. This therapy targets a protein called ROR1, found on some cancer cells, and aids the immune system in attacking the cancer. These early results suggest that LYL797 could be effective for cancers such as triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). ^{1 4 6 7 8}

Who Is on the Research Team?

Jackie Walling, MBChB, PhD

Principal Investigator

Lyell Immunopharma, Inc.

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am fully active or can carry out light work.

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

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

Exclusion Criteria

I am on long-term blood thinners like warfarin.

I do not have active, untreated brain cancer spread but stable, treated brain involvement is okay.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Dose-escalation phase to determine the recommended Phase 2 dose (RP2D) for LYL797

Up to 28 days

Dose-Expansion

Dose-expansion phase to test the RP2D in additional patients

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• LYL797

Trial Overview 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).

How Is the Trial Designed?

Group I: Experimental LYL797 Experimental Treatment 1 Intervention

ROR1-targeted CAR T cells

Who Is Running the Clinical Trial?

Lyell Immunopharma, Inc.

Lead Sponsor

Trials

5

Recruited

610+

Citations

1. cgtlive.com cgtlive.com/view/lyell-ror1-targeted-car-t-lyl797-attains-60-clinical-benefit-rate-high-dose-level-phase-1-solid-tumor-trial

Lyell's ROR1-Targeted CAR-T LYL797 Attains 60% ... LYL797, an autologous investigational ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy, has demonstrated a clinical benefit rate (CBR) of 60%.

2. lyell.com lyell.com/pdf/2024/SITCPoster_797_final.pdf

LYL797 Reprogrammed ROR-1 CAR T cells Demonstrate ... Translational data from an ongoing Phase 1 clinical trial of LYL797, a ROR1-targeted CAR T-cell product candidate, suggest T-cell reprogramming technologies can ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9981679/

Anti-ROR1 CAR-T cells: Architecture and performance - PMC ... lung and breast cancers and melanoma. Compared to conventional CAR-T cells, tandem CAR-T cells showed a higher cytotoxic effect and increased cytokine ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02754-5/pdf

777TiP Phase I study of LYL797, a ROR1-targeted CAR T- ... Results: A total of 7,127 patients treated with IO were evaluated. Median age was 67. (IQR 60-74), 42% were of female sex, and 58% had lung cancer. EM ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05274451

A Study to Investigate LYL797 in Adults With Solid Tumors This study will evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ relapsed or refractory triple ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A850

754 Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell ... LYL797 is an investigational, autologous ROR1-targeted CAR T-cell product enhanced with genetic and epigenetic reprogramming technologies.

7. ir.lyell.com ir.lyell.com/news-releases/news-release-details/lyell-immunopharma-reports-dose-dependent-clinical-activity

News Release Details These are promising initial clinical findings demonstrating that LYL797 ROR-1-targeted CAR T cells had dose-dependent antitumor clinical activity.

8. mayo.edu mayo.edu/research/clinical-trials/cls-20537302

A Study to Investigate LYL797 in Adults With Solid Tumors The purpose of this study is to evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ ...