TBio-4101 + Pembrolizumab for Advanced Solid Cancers

(STARLING Trial)

Recruiting at 13 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

31 Participants Needed

Trial Summary

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.

What data supports the idea that TBio-4101 + Pembrolizumab for Advanced Solid Cancers is an effective treatment?

The available research shows that pembrolizumab, a part of the TBio-4101 + Pembrolizumab treatment, has shown positive results in treating various solid tumors, including non-small cell lung cancer and melanoma. For instance, in non-small cell lung cancer, patients treated with pembrolizumab had longer periods without the disease getting worse and lived longer overall compared to those who did not receive the treatment. This suggests that the combination of TBio-4101 and pembrolizumab could be effective for advanced solid cancers. ^{1 2 3 4 5}

What safety data is available for TBio-4101 and Pembrolizumab in treating advanced solid cancers?

Pembrolizumab, also known as KEYTRUDA or MK-3475, has been evaluated in various clinical trials for different cancers. Safety data from these trials indicate common immune-mediated adverse reactions such as hypothyroidism, pneumonitis, and hyperthyroidism. Other frequent adverse reactions include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. These findings are based on trials for conditions like non-small cell lung cancer, metastatic melanoma, and bladder cancer. The safety profile of TBio-4101, also known as TIDAL-01 or tumor-infiltrating lymphocyte therapy by Turnstone Biologics, is not detailed in the provided research, suggesting a need for further specific studies on this combination treatment. ^{1 2 6 7 8}

Is the drug Pembrolizumab a promising treatment for advanced solid cancers?

Yes, Pembrolizumab is a promising drug for advanced solid cancers. It has shown positive results in treating various solid tumors, including lung cancer and melanoma, by helping the immune system fight cancer cells more effectively. ^{1 2 5 9 10}

What is the purpose of this trial?

A multicenter trial to investigate TBio-4101, an autologous, neoantigen-selected, tumor-reactive TIL product, in patients with advanced solid malignancies.

Research Team

Ines Verdon, MD

Principal Investigator

Turnstone Biologics, Corp.

Eligibility Criteria

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.

My heart's pumping ability is reduced.

Additional exclusion criteria exist

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. England 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. [2021]

4. Switzerland 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. [2023]

5. United States 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. [2023]

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

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

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

9. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. [2022]