TBio-6517 + Pembrolizumab for Solid Tumors

(RAPTOR Trial)

No longer recruiting at 12 trial locations

Overseen By Huguette A Graham

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Turnstone Biologics, Corp.

Must not be taking: Oncolytic viruses, Immunosuppressants

Disqualifiers: CNS metastases, Cardiovascular disease, HIV/AIDS, 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: 7

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TBio-6517, both alone and with pembrolizumab (KEYTRUDA, an immunotherapy drug), to evaluate its effectiveness against solid tumors. Researchers aim to determine the optimal dose for future studies. Individuals with solid tumors that other treatments cannot cure might be suitable candidates, particularly if they can tolerate injections directly into their tumors. Participants will receive treatments through injections or IV infusions. The study explores various cancers, including melanoma and colorectal cancer. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you have not had any systemic therapy, surgery, or radiation therapy within the last 4 weeks, and you must have recovered from any acute side effects. If you are on anti-platelet or anti-coagulant therapy, it must be safely suspended for the trial procedures. Additionally, you should not have taken immunosuppressive medication within the last 4 weeks.

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

Research has shown that TBio-6517 underwent testing in earlier studies. Some unwanted side effects occurred, but overall, the data supports its safety in patients with advanced cancers. These trials remain in the early stages, so researchers are closely monitoring safety.

Pembrolizumab, also known as Keytruda, is generally considered safe. It has been used in many trials and is already approved for other conditions. However, it can cause side effects like lung inflammation.

Researchers are testing TBio-6517 and Pembrolizumab together to assess their safety when used simultaneously. Early results suggest both are safe, but ongoing studies will provide more information. Participants are helping researchers learn about any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TBio-6517 because it offers a novel approach to treating solid tumors by directly injecting the treatment into the tumor itself. This method allows for higher local concentrations of the drug, potentially enhancing its effectiveness while minimizing systemic side effects. When combined with pembrolizumab, a well-known immunotherapy, TBio-6517 may boost the immune system's ability to recognize and attack cancer cells more effectively. This combination targets the tumor in a way that could potentially increase the treatment's overall impact compared to current therapies.

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

This trial will evaluate the effectiveness of TBio-6517 and pembrolizumab in treating solid tumors. Studies have shown that pembrolizumab, a drug that helps the immune system fight cancer, effectively treats various solid tumors, especially in patients with certain markers. In this trial, some participants will receive TBio-6517 alone, while others will receive a combination of TBio-6517 and pembrolizumab. Research indicates that combining TBio-6517 with pembrolizumab enhances the immune system's ability to find and attack cancer cells. Early findings suggest that this combination is safe, with only about one-third of patients experiencing moderate side effects. Although TBio-6517 is new, it is designed to strengthen the immune response against tumors, showing promise in early studies. This combination could offer a new way to effectively treat different solid tumors. ^{4 5 6 7 8}

Who Is on the Research Team?

Ines Verdon, MD

Principal Investigator

Turnstone Biologics

Are You a Good Fit for This Trial?

Inclusion Criteria

You have a solid tumor that has spread and cannot be cured with standard treatments.

Your disease can be measured using specific criteria.

You have at least one tumor that can be safely injected and biopsied.

Exclusion Criteria

You have had inflammation of the heart muscle before.

You have any type of heart or blood vessel disease, even if you don't have any symptoms.

Prior systemic therapy, including experimental, surgery or radiation therapy within 4 weeks and must have recovered from acute toxicity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 dose escalation of TBio-6517 alone and in combination with pembrolizumab to determine the recommended Phase 2 dose (RP2D)

4 weeks

4 visits (in-person)

Treatment

Phase 2a treatment with TBio-6517 and pembrolizumab in various cancer types, with booster injections permitted for up to 24 months

24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

25 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• TBio-6517

How Is the Trial Designed?

Group I: TBio-6517 and Pembrolizumab in cutaneous squamous cell carcinoma of the skin Experimental Treatment 2 Interventions

Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 8 given every 3 weeks for up to 24 months in patients with cSCC. Booster injections of TBio-6517 are permitted for up to 24 months.

Group II: TBio-6517 and Pembrolizumab in cutaneous melanoma Experimental Treatment 2 Interventions

Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 given every 3 weeks for up to 24 months in patients with malignant melanoma of the skin. Booster injections of TBio-6517 are permitted for up to 24 months.

Group III: TBio-6517 and Pembrolizumab in MSS-CRC Experimental Treatment 2 Interventions

Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 given every 3 weeks for up to 24 months in patients with microsatellite stable colorectal carcinoma (MSS-CRC). Booster injections of TBio-6517 are permitted for up to 24 months.

Group IV: TBio-6517 and Pembrolizumab in HPV positive head and neck cancer Experimental Treatment 2 Interventions

Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 9 given every 3 weeks for up to 24 months in patients with HPV associated oropharyngeal cancer. Booster injections of TBio-6517 are permitted for up to 24 months.

Group V: Arm D: TBio-6517 intravenous and Pembrolizumab Experimental Treatment 2 Interventions

Dose escalation of TBio-6517 administered in combination with pembrolizumab. Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months. Pembrolizumab will be administered beginning at Day 9 via intravenous (IV) infusion every 3 weeks for up to 24 months.

Group VI: Arm C: TBio-6517 intravenous Experimental Treatment 1 Intervention

Dose escalation of TBio-6517 alone administered by intravenous infusion x 4. Booster infusions of TBio-6517 are permitted for up to 24 months.

Group VII: Arm B: TBio-6517 and Pembrolizumab Experimental Treatment 2 Interventions

Dose escalation of TBio-6517 administered in combination with pembrolizumab. TBio-6517 will be directly injected into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months. Pembrolizumab will be administered beginning at Day 9 via intravenous (IV) infusion every 3 weeks for up to 24 months.

Group VIII: Arm A: TBio-6517 alone Experimental Treatment 1 Intervention

Dose escalation of TBio-6517 alone administered by direct injection into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months.

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+

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

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]

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., 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]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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 is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

The maximum tolerated doses (MTDs) for the combination of pembrolizumab and trametinib were established, with concurrent dosing showing a lower objective response rate (0%) compared to intermittent dosing (27%).

While the combination treatment had manageable safety profiles, with 31% of patients experiencing grade 3/4 treatment-related adverse events in the concurrent group, the overall antitumor activity was limited, suggesting that this combination may not be highly effective for solid tumors and BRAF wild-type melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Maio, M., Carlino, MS., Joshua, AM., et al.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04301011

NCT04301011 | Study of TBio-6517 Given Alone or in ... This is a Phase 1/2a dose escalation study with TBio-6517 administered by direct injection into tumor(s) or by intravenous infusion.

2. withpower.com withpower.com/trial/phase-2-triple-negative-breast-neoplasms-5-2020-6ee32

TBio-6517 + Pembrolizumab for Solid Tumors (RAPTOR ... Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non- ...

3. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct04301011

A Phase I/IIa, Multicenter, Open-label Trial of TBio-6517, an ... By taking part in a clinical trial, you have access to potentially effective treatments not available elsewhere. Additionally, you will contribute to cancer ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482737/

Transforming cancer immunotherapy: integration of distinct ... These approaches demonstrate strong synergistic effects in enhancing tumor immune recognition, overcoming resistance to monotherapies, and ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20490405

Study of TBio-6517, Given Intratumorally, Alone or in ... The purpose of this study is to determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04301011

NCT04301011 | Study of TBio-6517 Given Alone or in ... This is a Phase 1/2a dose escalation study with TBio-6517 administered by direct injection into tumor(s) or by intravenous infusion.

7. umiamihealth.org umiamihealth.org/en/sylvester-comprehensive-cancer-center/clinical-trials/trials/study-of-tbio-6517-given-alone-or-in-combination-with-pembrolizumab-in-solid-tumors-20200277

Study of TBio-6517 Given Alone or in Combination With ... Study of TBio-6517 Given Alone or in Combination With Pembrolizumab in Solid Tumors ... - At least one tumor amenable to safe ITu injections and biopsies

8. epa.govt.nz epa.govt.nz/assets/FileAPI/hsno-ar/APP204138/APP204138-EPA-staff-assessment-report.pdf

Staff Assessment Report TBio-6517 were considered adverse. This data supports the safety of TBio-6517 in the study of patients with advanced cancers. 48. The EPA ...