TBio-4101 + Pembrolizumab for Advanced Solid Cancers

(STARLING Trial)

No longer recruiting at 14 trial locations

Overseen By Catherine Barker

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Turnstone Biologics, Corp.

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: Active malignancy, Immunodeficiency, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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 approach for various advanced solid cancers, using a combination of TBio-4101, a personalized immune cell therapy, and pembrolizumab, a cancer-fighting drug. Researchers aim to determine the effectiveness of this combination for cancers such as colorectal, lung, breast, and melanoma that have not responded to standard treatments. The trial includes different groups for each cancer type, allowing researchers to study the response of each group to the treatment. Individuals who have tried other cancer treatments without success and have specific types of cancer may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic anti-coagulant therapy, it must be discontinued or temporarily changed. Also, if you are on chronic systemic steroid therapy or any other form of immunosuppressive treatment, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, a drug used in this trial, has already received approval for treating several types of cancer, such as head and neck cancer and non-small cell lung cancer. This indicates it is generally well-tolerated when used alone. However, side effects like fatigue, nausea, and skin rash can occur.

For TBio-4101, limited information exists because it remains in early testing. This phase primarily assesses safety, aiming to identify any common or serious side effects. Although the full safety profile is not yet known, this treatment employs special immune cells called tumor-infiltrating lymphocytes (TILs) to attack cancer. This promising therapy requires careful monitoring for side effects.

Participants should be aware that the safety of TBio-4101 is still under study. Both treatments aim to enhance the immune system's ability to fight cancer, which is an exciting approach, but potential risks should be considered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TBio-4101 combined with Pembrolizumab because it offers a new approach in targeting advanced solid cancers. Unlike traditional therapies that might focus solely on disrupting cancer cell growth, TBio-4101 is designed to enhance the body's immune response specifically against tumor cells. Pembrolizumab, a known PD-1 inhibitor, works by freeing up the immune system to attack cancer more effectively, and when paired with TBio-4101, it could potentially amplify this immune response. This dual-action strategy aims to tackle cancers that have resisted standard treatments like chemotherapy or other PD-1 inhibitors, providing hope for better outcomes in challenging cases such as non-small cell lung cancer, colorectal carcinoma, and breast cancer, among others.

What evidence suggests that this trial's treatments could be effective for advanced solid cancers?

In this trial, participants will receive a combination of pembrolizumab and TBio-4101 to treat various advanced solid cancers. Previous studies have shown that pembrolizumab effectively treats several types of solid tumors, such as head and neck cancer and non-small cell lung cancer, by enhancing the immune system's ability to fight cancer cells. Research indicates that therapies like TBio-4101, which use the patient's own immune cells, can also boost the immune system's capacity to target and destroy cancer cells. Early findings suggest that combining pembrolizumab with TBio-4101 could enhance effectiveness against solid cancers. Although detailed human data on TBio-4101 remains limited, its mechanism appears promising for treating difficult cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Ines Verdon, MD

Principal Investigator

Turnstone Biologics, Corp.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers (like breast, colorectal, melanoma, lung cancer) that haven't responded to standard treatments. They must have a lesion measurable for response assessment and a tumor suitable for TIL production. Good organ function and an ECOG status of 0 or 1 are required. Those with heart issues, other active cancers in the last 3 years, immune deficiencies, severe infections like HIV/HBV/HCV/CMV/WNV/HTLV I/II/syphilis or brain metastases aren't eligible.

Inclusion Criteria

My cancer has not responded to standard treatments.

My organs are functioning well.

Additional inclusion criteria exist

Exclusion Criteria

I have had a cell therapy or organ transplant before.

Additional exclusion criteria exist

My heart's pumping ability is reduced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Non-myeloablative chemotherapy is administered prior to TIL infusion

2 weeks

TIL and IL-2 Infusion

Participants receive TIL plus IL-2 infusion following chemotherapy

1 week

Radiation

Low-dose radiation therapy is administered prior to and after TIL plus IL-2 infusion

1 week

Pembrolizumab Treatment

Pembrolizumab is provided after the resolution of IL-2 toxicities

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

25 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• TBio-4101

Trial Overview The study tests TBio-4101 (a personalized T-cell therapy made from the patient's own tumor cells) combined with Pembrolizumab (an immunotherapy drug). It aims to see if this combo can help patients whose solid tumors didn't improve after standard care.

How Is the Trial Designed?

Group I: Uveal Melanoma Experimental Treatment 2 Interventions

Patients with advanced, metastatic uveal melanoma.

Group II: Non-Small Cell Lung Cancer Experimental Treatment 2 Interventions

Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.

Group III: Head and Neck Squamous Cell Carcinoma Experimental Treatment 2 Interventions

* Patients with head and neck squamous cell carcinoma who have received no prior therapy for metastatic disease * Patients with head and neck squamous cell carcinoma who are PD-1/PD-L1 inhibitor naïve at the time of TIL harvest and will be treated with TBio-4101 at the time of progression, inadequate response or intolerance to the PD-1/PD-L1 inhibitor-based standard of care regimen given on study.

Group IV: Cutaneous Melanoma Experimental Treatment 2 Interventions

Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.

Group V: Colorectal carcinoma Experimental Treatment 2 Interventions

Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.

Group VI: Breast Cancer Experimental Treatment 2 Interventions

Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Turnstone Biologics, Corp.

Lead Sponsor

Trials

7

Recruited

120+

Published Research Related to This Trial

The first-in-human study of MK-4830, a novel IgG4 monoclonal antibody targeting the ILT4 receptor, showed it was well tolerated with no dose-limiting toxicities among 84 patients with advanced solid tumors.

In combination with pembrolizumab, MK-4830 demonstrated promising antitumor activity, with 11 out of 34 patients achieving objective responses, including some who had previously progressed on other therapies, suggesting enhanced effectiveness in certain tumor microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. Siu, LL., Wang, D., Hilton, J., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

A 70-year-old woman developed immune checkpoint inhibitor (ICI)-related myocarditis and new-onset myasthenia gravis (MG) after starting pembrolizumab for metastatic thymic cancer, highlighting potential serious side effects of this treatment.

Despite the adverse effects, the patient showed significant improvement in her metastatic disease after 6 weeks, indicating that pembrolizumab can be effective in reducing tumor burden even in the presence of severe immune-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Szuchan, C., Elson, L., Alley, E., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

In a study of 42 patients with non-small-cell lung cancer treated with pembrolizumab, higher baseline levels of the proteins Fas ligand (FASLG) and inducible T-cell co-stimulator ligand (ICOSLG) were associated with significantly longer progression-free survival (PFS) and overall survival (OS).

Patients with high expressions of FASLG and ICOSLG who also had no detectable circulating tumor DNA (ctDNA) mutations after treatment initiation experienced even greater improvements in PFS and OS, suggesting these biomarkers could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Immune Proteins and Circulating Tumor DNA Predict the Clinical Outcome for Non-Small-Cell Lung Cancer Treated with an Immune Checkpoint Inhibitor. Stensgaard, S., Thomsen, A., Helstrup, S., et al.[2023]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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