Pembrolizumab + Sacituzumab Tirumotecan for Lung Cancer

(TroFuse-019 Trial)

Recruiting at 209 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals, HBV antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Severe cardiovascular disease, Active autoimmune, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will assess if adding sacituzumab tirumotecan with pembrolizumab after surgery is effective in treating NSCLC for participants not achieving pathological complete response. The primary hypothesis of this study is sacituzumab tirumotecan plus pembrolizumab is superior to pembrolizumab monotherapy with respect to disease free survival (DFS) as assessed by blinded independent central review (BICR).

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 immunosuppressive therapy or have received certain treatments like live vaccines or investigational agents recently, you may need to stop or adjust those before starting the trial.

What data supports the effectiveness of the drug Pembrolizumab + Sacituzumab Tirumotecan for lung cancer?

Pembrolizumab, a part of the treatment, has been shown to improve survival in patients with non-small cell lung cancer, especially when tumors express a specific protein called PD-L1. It has been approved by the FDA for treating certain types of lung cancer, demonstrating significant improvements in survival compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Sacituzumab Tirumotecan safe for humans?

Pembrolizumab, also known as Keytruda, has been used in treating various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as inflammation of the lungs, liver, or thyroid problems. Sacituzumab Tirumotecan, also known as SKB264 or MK-2870, does not have specific safety data available in the provided research, so it's important to discuss potential risks with your healthcare provider. ^{1 2 5 6 7}

How is the drug Pembrolizumab + Sacituzumab Tirumotecan unique for lung cancer treatment?

Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells and is already used for various cancers, including lung cancer. Sacituzumab Tirumotecan is a newer component that combines an antibody with a chemotherapy drug to target and kill cancer cells more effectively. This combination aims to enhance the immune response while directly targeting cancer cells, offering a potentially more effective treatment option for lung cancer. ^{1 2 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with a type of lung cancer called NSCLC who haven't fully responded to surgery. Participants should not have achieved complete removal of cancer (pCR). They must be healthy enough for further treatment.

Inclusion Criteria

My HIV is well controlled with medication.

My cancer was still present after surgery, according to the pathology report.

I can receive pembrolizumab and platinum-based chemotherapy before surgery.

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

My cancer is either NSCLC, LCNEC, sarcomatoid, SCLC with small cell elements, or has ALK gene changes.

I have been treated for an autoimmune disease in the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab and double-platinum chemotherapy prior to surgery

12 weeks

4 visits (in-person)

Surgery

Participants undergo surgery after neoadjuvant treatment

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive sacituzumab tirumotecan with pembrolizumab or pembrolizumab monotherapy

42 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

93 months

Treatment Details

Interventions

• MK-2870 (Other)
• Pembrolizumab (Checkpoint Inhibitor)

Trial Overview The study tests if MK-2870 combined with pembrolizumab improves disease-free survival compared to using pembrolizumab alone after surgery in NSCLC patients without pCR. It's a comparison between two potential post-surgery treatments.

Participant Groups

Group I: Pembrolizumab + Sacituzumab tirumotecan Experimental Treatment 3 Interventions

Participants will receive pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by sacituzumab tirumotecan 4 mg/kg IV infusion every 2 weeks (Q2W) for up to 12 doses (\~24 weeks) with pembrolizumab monotherapy 200 mg IV infusion every 6 weeks (Q6W) for up to 7 cycles (\~42 weeks).

Group II: Pembrolizumab Active Control 6 Interventions

Participants will receive pembrolizumab 200 mg intravenous (IV) infusion Q3W for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by pembrolizumab monotherapy 200 mg IV infusion Q6W for up to 7 cycles (\~42 weeks).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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 (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., 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]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

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]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. France pubmed.ncbi.nlm.nih.gov

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

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

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]

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

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

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

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

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

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. [2020]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

9. England 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. [2022]