LYL845 for Solid Cancers

No longer recruiting at 18 trial locations

Overseen By Vandana Mathur, MD, FASN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lyell Immunopharma, Inc.

Must not be taking: Systemic corticosteroids, Chronic anticoagulants

Disqualifiers: CNS involvement, Active infection, Autoimmune, 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 a new treatment called LYL845 (experimental treatment) for individuals with certain types of cancer that have returned or not responded to other treatments. The focus is on melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The trial aims to assess the safety and effectiveness of this treatment against tumors. Suitable candidates have one of these cancers that has spread or cannot be surgically removed and have already tried standard treatments without success. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids at a dose greater than 10 mg of prednisone per day or require chronic anticoagulation, you may not be eligible to participate.

Is there any evidence suggesting that LYL845 is likely to be safe for humans?

Research shows that LYL845, a new treatment using special immune cells called tumor infiltrating lymphocytes (TILs), is being tested for safety. This treatment is in the early testing stages, so limited safety information is available. However, similar TIL treatments have generally been well-tolerated in other studies. The goal is to find a dose that is both safe and effective.

In these studies, side effects can occur but are usually manageable. Common side effects of TIL therapies might include fever, chills, or fatigue. Notably, LYL845 has received Orphan Drug Designation from the FDA, which sometimes suggests promise for treating serious conditions. However, since this is an early phase trial, researchers are closely monitoring and evaluating safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LYL845 because it represents a novel approach to treating solid cancers. Unlike traditional cancer treatments like chemotherapy or radiation that target cancer cells broadly, LYL845 uses epigenetically reprogrammed tumor infiltrating lymphocytes (TILs). This means it leverages the body's own immune cells, which are modified to better recognize and attack cancer cells. This targeted approach could potentially offer more precise treatment with fewer side effects, making it a promising option for patients with solid tumors.

What evidence suggests that LYL845 might be an effective treatment for solid cancers?

Research has shown that LYL845, a new therapy using special immune cells, could help treat solid cancers. This therapy takes cells from a patient's tumor, enhances them, and reintroduces them into the body to combat cancer. Studies have found that this approach can be effective, particularly for advanced melanoma, often outperforming current treatments. LYL845 enhances these cells by using a special process to boost their cancer-fighting ability. Early results suggest LYL845 might improve the immune response against difficult cancers like non-small cell lung cancer and colorectal cancer. While more research is needed, these findings offer hope for better outcomes in patients with these challenging conditions. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-75 with advanced melanoma, NSCLC, or CRC that's relapsed/refractory after prior treatments can join. They need at least one resectable tumor lesion and must use effective contraception. Exclusions include other cancers within 3 years, certain blood thinners, pregnancy/nursing, uncontrolled effusions/ascites, active autoimmune diseases or infections, high-dose steroids (>10 mg prednisone/day), previous cell therapy or organ transplants.

Inclusion Criteria

I am fully active or can carry out light work.

I have a cancer lesion that can be removed and another that can be measured and biopsied.

I am capable of becoming pregnant and have a negative pregnancy test.

Exclusion Criteria

I have had cell therapy treatment before.

I have fluid buildup in my chest or abdomen that causes symptoms.

I have not had any other cancer within the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants with melanoma are enrolled to determine the recommended Phase 2 dose range (RP2DR)

Up to 2 years

Expansion Cohorts

Enrollment is expanded to include additional participants with melanoma, NSCLC, and CRC

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

• LYL845

Trial Overview LYL845 is being tested in this study to see if it's safe and works against tumors. It's a new type of TIL therapy for adults who've had their cancer come back or not respond to treatment. The trial involves increasing doses to find the right amount and will also look at how well it shrinks tumors in participants with melanoma, NSCLC, and CRC.

How Is the Trial Designed?

Group I: Experimental LYL845 Experimental Treatment 1 Intervention

Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

Who Is Running the Clinical Trial?

Lyell Immunopharma, Inc.

Lead Sponsor

Trials

5

Recruited

610+

Published Research Related to This Trial

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a phase I clinical trial, tumor-infiltrating lymphocyte therapy combined with nivolumab (an anti-PD-1 drug) was found to be safe and well-tolerated in patients with stage IV or recurrent non-small cell lung cancer.

The combination therapy showed preliminary signs of efficacy, suggesting it may be a promising treatment option for advanced lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-Infiltrating Lymphocytes Help Rein In NSCLC. [2021]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05573035

A Study to Investigate LYL845 in Adults With Solid Tumors This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, ...

2. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A843

747 Phase 1 trial of LYL845, an autologous tumor- ... LYL845 is an investigational autologous TIL therapy produced with Lyell's epigenetic reprogramming (Epi-R™) protocol, which generates ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393248/

Recent clinical researches and technological development in ... In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches.

4. astctjournal.org astctjournal.org/article/S2666-6367(24)00783-8/fulltext

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1465324924009708

Entering a new era of tumor-infiltrating lymphocyte cell ... All in all, outcomes achieved with TIL cell therapy compare favorably with current best available therapy in the second-line advanced melanoma and beyond, where ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20567314?p=1

A Study to Investigate LYL845 in Adults With Solid Tumors The purpose of this study is to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724007838

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier The first section explores several solid cancers that demonstrate the greatest potential for future indications of TIL therapy. The second section provides ...

8. ir.lyell.com ir.lyell.com/news-releases/news-release-details/lyell-immunopharma-receives-fda-orphan-drug-designation-lyl845

Lyell Immunopharma Receives FDA Orphan Drug ... The US Food and Drug Administration (FDA) granted Orphan Drug Designation to LYL845, an investigational tumor infiltrating lymphocyte (TIL) product candidate.