Pembrolizumab + Sacituzumab Tirumotecan for Lung Cancer

Recruiting at 262 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Small cell lung cancer, Cardiovascular disease, Autoimmune disease, 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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

851 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of medications, including pembrolizumab (an immunotherapy drug) and sacituzumab tirumotecan (an experimental treatment), to determine if they can improve survival rates for people with advanced squamous non-small cell lung cancer. Researchers compare two treatment plans: one with both pembrolizumab and sacituzumab tirumotecan, and another with just pembrolizumab. The goal is to identify which approach helps patients live longer. This study suits those diagnosed with advanced squamous non-small cell lung cancer who have not received treatment for their metastatic condition. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any strong inducers or inhibitors of CYP3A4 (a liver enzyme that affects drug metabolism) at least 2 weeks before starting the study medication. Other than this, the protocol does not specify if you need to stop other medications.

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

Research shows that pembrolizumab is generally safe for patients, with many using it for various types of cancer. Common side effects include fatigue, itching, and nausea, but these are usually manageable.

Sacituzumab tirumotecan is a newer drug still under study. Early research suggests that, when combined with pembrolizumab, it may help slow disease progression. The FDA has shown special interest in it, highlighting its potential. However, caution is necessary as more safety information is still being collected. Earlier studies noted side effects such as low blood cell counts and diarrhea, but the full range of possible side effects is still under investigation.

Overall, while the evidence is promising, joining a trial involves some uncertainty about side effects. Patients should always consult healthcare providers to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine innovative approaches to tackle lung cancer. Pembrolizumab is already well-known for targeting PD-1, a protein that helps cancer cells hide from the immune system, but when paired with sacituzumab tirumotecan (sac-TMT), it introduces a novel mechanism. Sac-TMT is a type of antibody-drug conjugate that delivers chemotherapy directly to the cancer cells, potentially boosting the effectiveness of the immune response initiated by Pembrolizumab. This combination could potentially offer a more targeted and robust attack on lung cancer cells compared to standard chemotherapy and immunotherapy regimens.

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

This trial will compare two treatment approaches for lung cancer. In one arm, participants will receive a combination of sacituzumab tirumotecan (sac-TMT) and pembrolizumab. Studies have shown that this combination may benefit lung cancer treatment by significantly extending the time patients live without their cancer growing or spreading. Sac-TMT has demonstrated promising results in treating advanced non-small cell lung cancer (NSCLC) and is generally safe to use. In the other arm, participants will receive pembrolizumab monotherapy, which is already known to help the immune system attack certain types of lung cancer. Adding sac-TMT appears to enhance this effect, potentially leading to better outcomes for patients. ^{1 2 5 6 7}

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 specific type of advanced lung cancer called metastatic squamous NSCLC. They must have good organ function, provide a tumor tissue sample, and have measurable disease. People with controlled hepatitis B or C can join; those with HIV must be stable on ART. It's not suitable for individuals who haven't recovered from previous cancer treatment side effects.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have provided a sample of my tumor that has not been treated with radiation.

I have HIV and it is well controlled with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive pembrolizumab in combination with carboplatin and paclitaxel or nab-paclitaxel for 4 cycles

12 weeks

4 visits (in-person, every 3 weeks)

Maintenance

Participants receive pembrolizumab with or without sacituzumab tirumotecan until discontinuation criteria are met

96 weeks

Visits every 6 weeks for pembrolizumab, every 2 weeks for sac-TMT

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 79 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• sac-TMT

Trial Overview The study tests pembrolizumab combined with chemotherapy (carboplatin/taxane), followed by either continued pembrolizumab alone or with an additional drug called sacituzumab tirumotecan (sac-TMT). The goal is to see if adding sac-TMT improves survival compared to just pembrolizumab after initial treatment.

How Is the Trial Designed?

Group I: Maintenance Arm A: Pembrolizumab + sac-TMT Experimental Treatment 5 Interventions

During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.

Group II: Maintenance Arm B: Pembrolizumab Monotherapy Active Control 4 Interventions

During the induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.

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?

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

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., 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]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., 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]

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 (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]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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]

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. 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 ...

3. onclive.com onclive.com/view/sacituzumab-tirumotecan-plus-pembrolizumab-is-set-to-be-evaluated-in-tnbc

Sacituzumab Tirumotecan Plus Pembrolizumab Is Set to ... Prior data from the study revealed that sac-TMT significantly improved PFS compared with chemotherapy, with a 69% lower risk of disease ...

4. 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.

5. 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 ...

6. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06422143/

MK2870-023 - MSD Clinical Trials It is hypothesized that pembrolizumab with maintenance sacituzumab tirumotecan is superior to pembrolizumab without sacituzumab tirumotecan maintenance with ...

7. merck.com merck.com/news/fda-grants-breakthrough-therapy-designation-to-sacituzumab-tirumotecan-sac-tmt-for-the-treatment-of-certain-patients-with-previously-treated-advanced-or-metastatic-nonsquamous-non-small-cell-lung-ca/

FDA Grants Breakthrough Therapy Designation to ... This designation is based on data from the Phase 2 expansion cohort of a Phase 1/2 study evaluating sac-TMT in patients with EGFR-mutated NSCLC, ...