LYL845 for Solid Cancers

Recruiting at 17 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

108 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

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.

What safety data is available for LYL845 or similar treatments in humans?

The safety of treatments similar to LYL845, such as PD-1/PD-L1 inhibitors, has been studied in various cancers. These treatments have shown some toxic events, but they are generally considered safe and tolerable in humans, with specific management strategies for any adverse effects. ^{1 2 3 4 5}

How does the drug LYL845 work differently for solid cancers?

LYL845 is unique because it targets the lipolysis-stimulated lipoprotein receptor (LSR), which is a novel immune checkpoint molecule found in various solid tumors. This drug works by enhancing the immune system's ability to fight cancer by increasing the activity of CD8+ T cells, which are crucial for attacking cancer cells. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

3. Germany 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody-Drug Conjugates. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Tumor cell-expressed lipolysis-stimulated lipoprotein receptor negatively regulates T-cell function. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

LRP8 is overexpressed in estrogen-negative breast cancers and a potential target for these tumors. [2021]

10. China pubmed.ncbi.nlm.nih.gov

[Clinical significance of the expression of lung resistance protein in non-small cell lung carcinomas]. [2017]