Sacituzumab Tirumotecan + Pembrolizumab for Lung Cancer

(TroFuse-007 Trial)

Recruiting at 292 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Small cell lung cancer, Cardiovascular disease, CNS metastases, 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: 6

Duration: 108 weeks

614 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining sacituzumab tirumotecan (an experimental treatment also known as SKB264 or MK-2870) with pembrolizumab can extend the lives of people with certain types of lung cancer compared to using pembrolizumab alone. The study targets non-small cell lung cancer (NSCLC) that cannot be treated with specific existing therapies and where the cancer cells exhibit a specific marker (PD-L1 expression) in a significant portion of the tumor. It may suit those diagnosed with this type of lung cancer who have not received certain prior treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial requires that you do not take strong inhibitors or inducers of CYP3A4 (a liver enzyme) at least 14 days before starting the study and throughout the study. If you are on such medications, you may need to stop or switch them.

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

Research has shown that the combination of sacituzumab tirumotecan and pembrolizumab is generally well-tolerated. In earlier studies, patients who took these two drugs together experienced manageable side effects, meaning they were not severe and could be controlled.

Pembrolizumab alone has FDA approval for treating other types of cancer, indicating its general safety for humans. However, when combined with sacituzumab tirumotecan, the safety profile might differ. Early results suggest the combination remains acceptable.

Overall, the safety data for this treatment combination is promising, indicating participants can expect a reasonable level of safety with non-severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Tirumotecan combined with Pembrolizumab for lung cancer because it introduces a novel approach to treatment. Sacituzumab Tirumotecan is an antibody-drug conjugate, which means it delivers a chemotherapy drug directly to cancer cells, potentially reducing side effects and increasing effectiveness compared to traditional chemotherapy. Meanwhile, Pembrolizumab is an established immunotherapy that helps the immune system better recognize and attack cancer cells. This combination aims to enhance treatment effectiveness by simultaneously targeting cancer cells directly and boosting the body's immune response.

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

In this trial, participants will receive either a combination of sacituzumab tirumotecan and pembrolizumab or pembrolizumab alone. Research has shown that combining sacituzumab tirumotecan and pembrolizumab may effectively treat lung cancer. One study found this combination worked well for patients with advanced non-small cell lung cancer (NSCLC). Early results suggest that using both drugs together might extend patient survival compared to pembrolizumab alone. Sacituzumab tirumotecan targets cancer cells directly, potentially enhancing treatment effectiveness. Pembrolizumab is already known for helping the immune system fight cancer. Together, these drugs could offer a strong new treatment option for people with lung cancer. ^{1 2 4 5 6}

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 advanced non-small cell lung cancer (NSCLC) showing high PD-L1 expression in tumors. Candidates must have a life expectancy of over 3 months, controlled HIV if present, and no need for EGFR-, ALK-, or ROS1-targeted primary therapy. They should be physically able to perform daily activities with little or no assistance.

Inclusion Criteria

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

My cancer is not suitable for EGFR, ALK, or ROS1-targeted treatments.

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

Treatment

Participants receive sacituzumab tirumotecan and pembrolizumab or pembrolizumab alone for 18 cycles

108 weeks

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Open-label extension (optional)

Participants may receive up to an additional 9 cycles of pembrolizumab monotherapy if there is progressive disease

54 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-2870
• Pembrolizumab

Trial Overview The study aims to see if MK-2870 combined with pembrolizumab improves survival compared to using pembrolizumab alone in patients. Participants who show disease progression after initial treatment may receive additional cycles of pembrolizumab monotherapy.

How Is the Trial Designed?

Group I: Pembrolizumab + Sacituzumab tirumotecan Experimental Treatment 3 Interventions

Participants receive sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle + 400 mg Pembrolizumab every 6 weeks (q6w) via IV infusion on Day 1 of each 6-week cycle for 18 cycles. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.

Group II: Pembrolizumab Active Control 2 Interventions

Participants receive 400 mg Pembrolizumab via IV infusion q6w on Day 1 of each 6-week cycle for 18 cycles

MK-2870 is already approved in China for the following indications:

Approved in China as Sacituzumab Tirumotecan for:

• Unresectable locally advanced or metastatic triple-negative breast cancer

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

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, 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]

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 Ib study involving 64 patients with Stage IV non-small cell lung cancer (NSCLC), the combination of necitumumab and pembrolizumab showed a confirmed overall response rate of 23.4%, indicating modest efficacy in this patient population.

The treatment was well-tolerated, with no dose-limiting toxicities reported, and the safety profile was consistent with typical effects of epidermal growth factor receptor inhibitors and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. Besse, B., Garrido, P., Cortot, AB., et al.[2021]

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]

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, 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]

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]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

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

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

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

716MO Efficacy and safety of sacituzumab tirumotecan ... Sac-TMT 3 or 5 mg/kg Q2W+ pembrolizumab 400 mg Q6W were assessed in safety run-in period and the doses deemed well tolerated were being explored in expansion ...