TATE + Pembrolizumab for Lung Cancer

Recruiting at 3 trial locations

Overseen By Chiwei Lu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Teclison Ltd.

Disqualifiers: Organ transplant, CNS metastasis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with refractory metastatic colorectal cancer or non-small cell lung cancer with liver metastasis treated with Trans-arterial Tirapazamine Embolization along with Pembrolizumab.

Will I have to stop taking my current medications?

The trial requires that you have stopped chemotherapy at least 4 weeks before starting and be free from any chemo-related side effects. It doesn't specify about other medications, so you should discuss your current medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab for treating colorectal and lung cancer?

Pembrolizumab has shown clinical activity in treating non-small-cell lung cancer (NSCLC) and melanoma, with studies indicating it can help the immune system fight cancer cells. It is approved for use in certain lung cancers and melanoma, suggesting potential benefits for other cancers like colorectal. ^{1 2 3 4 5}

Is the combination of TATE and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) has been studied in various cancers, including lung and melanoma, and is generally considered safe, though it can cause side effects like fatigue, cough, and thyroid issues. Common immune-related side effects include inflammation of the lungs (pneumonitis) and thyroid problems. While specific safety data for the combination with TATE is not available, pembrolizumab alone has a known safety profile. ^{1 2 6 7 8}

What makes the TATE + Pembrolizumab treatment unique for colorectal and lung cancer?

The TATE + Pembrolizumab treatment is unique because it combines an immunotherapy drug, Pembrolizumab, with a novel approach called Trans-arterial Tirapazamine Embolization (TATE), which directly targets tumors through the blood vessels, potentially enhancing the effectiveness of the treatment compared to standard therapies. ^{9 10 11 12 13}

Research Team

Ray Lee

Principal Investigator

Teclison Limited

Eligibility Criteria

This trial is for adults with metastatic non-small cell lung cancer (NSCLC) who have already tried PD-1/PD-L1 inhibitors and chemotherapy. Patients whose disease has worsened after treatment are eligible to participate.

Inclusion Criteria

Have you received chemotherapy AND immunotherapy to treat your cancer?

Has your lung cancer spread to your liver?

Has your cancer progressed despite treatment?

Exclusion Criteria

I have not had major stomach or intestinal bleeding in the last 2 months.

My cancer has spread to my brain.

I have had an organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive Trans-arterial Tirapazamine Embolization (TATE) and Pembrolizumab or standard of care for mCRC cohort

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Pembrolizumab
• TATE

Trial Overview The study tests whether combining Tirapazamine with embolization could enhance anti-tumor immunity and make Pembrolizumab effective in lung cancer patients who have failed prior immunotherapy.

Participant Groups

Group I: colorectal cancer Experimental Treatment 3 Interventions

metastatic colorectal cancer progressed on at least two lines of chemotherapy

Group II: NSCLC Experimental Treatment 1 Intervention

Liver metastatic NSCLC progressed on immune checkpoint inhibitors and chemotherapy

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?

Teclison Ltd.

Lead Sponsor

Trials

4

Recruited

200+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

In a study involving 74 patients with advanced non-small-cell lung cancer, the combination of pembrolizumab with platinum-based chemotherapy showed promising antitumor activity, with objective response rates of 48% to 75% across different treatment cohorts.

The treatment was generally well-tolerated, with no dose-limiting toxicities reported, although 40% to 46% of patients experienced grade 3/4 adverse events, which aligns with the known side effects of platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. Gadgeel, SM., Stevenson, JP., Langer, CJ., et al.[2019]

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]

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]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

177Lu-PSMA617 therapy demonstrated high tumor doses in metastatic sites such as skeletal, lymph node, and liver metastases, indicating its potential efficacy in treating metastatic castration-resistant prostate cancer (mCRPC).

The therapy resulted in a significant decrease in PSMA uptake in most lesions after treatment cycles, suggesting a reduction in tumor activity, although individual responses varied, highlighting the need for personalized dosimetry in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates. Scarpa, L., Buxbaum, S., Kendler, D., et al.[2018]

The study demonstrates that 64Cu-PSMA-617, a radio-labeled imaging agent targeting prostate-specific membrane antigen (PSMA), can effectively visualize gastric adenocarcinoma in a mouse model, indicating its potential as a new tool for managing this type of cancer.

The imaging agent showed high stability and specificity, with successful tumor visualization in mice, suggesting that 64Cu-PSMA-617 could be a promising radio-tracer for not only prostate cancer but also other cancers expressing PSMA, such as gastric adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model. Han, XD., Liu, C., Liu, F., et al.[2022]

In two case studies, patients with advanced prostate cancer tolerated radioligand therapy (RLT) with 177Lu-PSMA well, showing no significant hematotoxicity, which suggests a favorable safety profile for this treatment.

One patient experienced a positive radiologic and biochemical response after RLT following olaparib treatment, while the other achieved stabilization of prostate-specific antigen levels after combining RLT with pembrolizumab, indicating potential efficacy of these combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Experiences with 177Lu-PSMA Therapy in Combination with Pembrolizumab or After Pretreatment with Olaparib in Single Patients. Prasad, V., Zengerling, F., Steinacker, JP., et al.[2022]

In a study of 168 patients undergoing 177Lu-PSMA therapy for metastatic castration-resistant prostate cancer, a higher PD-L2 signature was linked to significantly longer overall survival (OS), suggesting it may enhance treatment response.

Conversely, PD-L1 levels did not show a significant association with patient outcomes, indicating that PD-L2 may be a more relevant biomarker for predicting the efficacy of 177Lu-PSMA therapy, particularly in patients with lower LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. Handke, A., Kesch, C., Fendler, WP., et al.[2023]

In a study involving 43 men with metastatic castration-resistant prostate cancer, a single dose of lutetium-177-PSMA-617 followed by pembrolizumab maintenance was found to be safe, with only 5% of patients experiencing serious treatment-related adverse events.

The treatment showed promising efficacy, with 56% of patients in the second part of the study achieving a confirmed objective response, indicating potential for durable clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose 177Lu-PSMA-617 followed by maintenance pembrolizumab in patients with metastatic castration-resistant prostate cancer: an open-label, dose-expansion, phase 1 trial. Aggarwal, R., Starzinski, S., de Kouchkovsky, I., et al.[2023]

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

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

4. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. [2019]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

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

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

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

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates. [2018]

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

64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model. [2022]

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

First Experiences with 177Lu-PSMA Therapy in Combination with Pembrolizumab or After Pretreatment with Olaparib in Single Patients. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Single-dose 177Lu-PSMA-617 followed by maintenance pembrolizumab in patients with metastatic castration-resistant prostate cancer: an open-label, dose-expansion, phase 1 trial. [2023]