Pembrolizumab + Sacituzumab Tirumotecan for Lung Cancer

(TroFuse-019 Trial)

Recruiting at 315 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

780 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a combination of drugs to determine if it can prevent lung cancer from returning after surgery. It targets non-small cell lung cancer (NSCLC) patients who did not achieve a full response post-surgery. Participants will receive pembrolizumab (an immunotherapy drug) alone or with sacituzumab tirumotecan (also known as SKB264 or MK-2870, an experimental treatment) to assess which option better prolongs cancer-free periods. Ideal candidates have NSCLC that can be surgically removed and have not fully responded to initial treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research shows that combining sacituzumab tirumotecan and pembrolizumab is generally safe. Studies have found that patients can manage this treatment safely, with no new safety issues reported. Participants in these studies handled the treatment well, experiencing expected and manageable side effects. Sacituzumab tirumotecan has been tested with pembrolizumab in other contexts, and the safety data so far suggests it is well-tolerated. These findings indicate the treatment is likely safe, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, a well-known immunotherapy, with sacituzumab tirumotecan, a newer antibody-drug conjugate, to potentially enhance lung cancer treatment outcomes. Unlike the standard of care, which typically involves chemotherapy and pembrolizumab alone, this combination targets cancer cells more precisely by delivering a chemotherapy agent directly to the tumor cells via an antibody, potentially reducing side effects and improving effectiveness. This approach could offer a more potent attack on cancer cells, possibly leading to better patient outcomes and offering new hope for those battling lung cancer.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that using sacituzumab tirumotecan with pembrolizumab, which participants in this trial may receive, may treat non-small cell lung cancer (NSCLC) more effectively. Studies suggest this combination can lead to better results than pembrolizumab alone, another treatment arm in this trial. Specifically, the combination has shown promise in helping patients with advanced NSCLC and has manageable side effects. Adding sacituzumab tirumotecan might help patients remain disease-free longer after surgery. Overall, this combination is being tested for its potential to provide better outcomes than pembrolizumab alone. ^{2 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MK-2870
• Pembrolizumab

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06312137

NCT06312137 | A Study to Assess Efficacy and Safety of ... This study will assess if adding sacituzumab tirumotecan with pembrolizumab after surgery is effective in treating NSCLC for participants not achieving ...

2. jto.org jto.org/article/S1556-0864(24)01578-8/fulltext

P4.11D.02 Phase 3 Trofuse-007 Study The TroFuse-007 study will evaluate the efficacy and safety of the addition of sac-TMT to pembrolizumab vs pembrolizumab alone in patients with previously ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8502

Sacituzumab tirumotecan (SKB264/MK-2870) in ... SKB264 in combination with KL-A167 demonstrated promising efficacy results in treatment naive advanced NSCLC with manageable safety profile.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06049212

NCT06049212 | Sacituzumab Tirumotecan (MK-2870) as ... This is a phase 1 trial of the safety, tolerability, and pharmacokinetics (PK) of sacituzumab tirumotecan monotherapy, and of sacituzumab tirumotecan in ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20584396

Clinical Trials The primary objective of the study is to compare sacituzumab tirumotecan combined with pembrolizumab to pembrolizumab alone with respect to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06170788

NCT06170788 | Sacituzumab Tirumotecan (MK-2870) in ... The primary objective of the study is to compare sacituzumab tirumotecan combined with pembrolizumab to pembrolizumab alone with respect to overall survival ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02297-X/fulltext

716MO Efficacy and safety of sacituzumab tirumotecan ... Sac-TMT plus pembrolizumab demonstrated promising and durable antitumor activity with manageable safety profile. No new safety signal was observed. Considering ...

8. cancernetwork.com cancernetwork.com/view/sac-tmt-combo-produces-encouraging-activity-in-pretreated-metastatic-crpc

Sac-TMT Combo Produces Encouraging Activity in ... Combining sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) with pembrolizumab (Keytruda) demonstrated promising activity and a manageable ...