Sacituzumab Tirumotecan vs Standard Therapy for Lung Cancer

Recruiting at 161 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, Live vaccines, others

Disqualifiers: Squamous NSCLC, Cardiovascular disease, Pneumonitis, 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: 2

Duration: Up to approximately 51 months

520 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have recovered from adverse effects of previous cancer treatments and cannot have active infections requiring systemic therapy.

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

Carboplatin, a component of the treatment, has shown favorable survival rates in patients with advanced non-small-cell lung cancer (NSCLC) compared to its parent analogue cisplatin. Additionally, pemetrexed, another component, has been effective in treating relapsed NSCLC with similar response and survival outcomes to other treatments, but with less toxicity. ^{1 2 3 4 5}

Is Sacituzumab Tirumotecan safe for humans?

Pemetrexed, a component of the treatment, has been used safely in combination with other drugs for lung cancer and mesothelioma, but it can cause side effects like low blood cell counts, fatigue, and nausea. Carboplatin, another component, is generally safe but can also cause low blood cell counts and other side effects. Always consult with a healthcare provider for personalized advice. ^{6 7 8 9 10}

What makes the drug Sacituzumab Tirumotecan unique for lung cancer treatment?

Sacituzumab Tirumotecan is unique because it combines a targeted therapy approach with traditional chemotherapy, potentially offering a novel mechanism of action by delivering a potent chemotherapy agent directly to cancer cells, which may improve effectiveness and reduce side effects compared to standard therapies. ^{1 3 11 12 13}

What is the purpose of this trial?

The purpose of this study is to evaluate sacituzumab tirumotecan versus pemetrexed in combination with carboplatin for the treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Participants in this study have NSCLC that has continued to progress on prior treatment with EGFR tyrosine kinase inhibitors (TKIs). The primary hypotheses of this study are that sacituzumab tirumotecan is better than platinum-based doublet chemotherapy (pemetrexed and carboplatin) in regard to progression-free survival (PFS) and overall survival (OS).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced-stage nonsquamous NSCLC that has worsened despite EGFR tyrosine kinase inhibitors. Candidates must have a life expectancy of at least 3 months, controlled HIV or Hepatitis B/C if present, and recovered from previous cancer therapy side effects.

Inclusion Criteria

My lung cancer is advanced and not squamous cell type.

My HIV is well controlled with medication.

I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.

Exclusion Criteria

I am HIV-positive with a history of Kaposi's sarcoma or Castleman's Disease.

I am currently on medication for an infection.

I have not received a live vaccine within the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab tirumotecan or pemetrexed plus carboplatin until discontinuation criteria are met

Up to approximately 51 months

Every 2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 51 months

Treatment Details

Interventions

• Carboplatin
• Pemetrexed
• Sacituzumab Tirumotecan

Trial Overview The study compares sacituzumab tirumotecan to the combination of pemetrexed and carboplatin in treating advanced non-squamous NSCLC with EGFR mutations. It aims to see which treatment leads to longer survival without disease progression.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 6 Interventions

Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.

Group II: Pemetrexed Plus Carboplatin Active Control 2 Interventions

Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL\*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular 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

Findings from Research

A variety of new agents, including taxanes, gemcitabine, and irinotecan, have shown promise in early clinical studies for treating non-small-cell lung cancer (NSCLC), indicating potential for improved treatment options.

Cisplatin remains a key component in combination therapies for NSCLC, being tested alongside these new agents, radiation, and surgery in numerous trials to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in metastatic non-small-cell lung cancer. Sandler, A.[2022]

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

Recent advancements in therapies for non-small-cell lung cancer (NSCLC) are leading to better control of the disease, particularly as new treatments targeting specific molecular pathways are developed.

Current chemotherapy regimens, especially combinations of paclitaxel or gemcitabine with cisplatin or carboplatin, show significant efficacy compared to older treatments, and ongoing studies will further clarify their relative benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in non-small-cell lung cancer: a continuing perspective. Ruckdeschel, JC.[2005]

In a phase III study involving 676 patients with advanced non-small-cell lung cancer, the combination of cetuximab and taxane/carboplatin (TC) did not significantly improve progression-free survival compared to TC alone, with median PFS of 4.40 months versus 4.24 months.

However, the addition of cetuximab resulted in a significantly higher overall response rate (25.7% vs. 17.2%) and showed a trend towards improved overall survival (9.69 months vs. 8.38 months), although this did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. Lynch, TJ., Patel, T., Dreisbach, L., et al.[2022]

Pemetrexed is an effective treatment for relapsed or chemotherapy-refractory non-small cell lung cancer (NSCLC), showing similar response and survival rates to taxotere but with less toxicity.

When combined with platinum analogs or other chemotherapy agents like gemcitabine or vinorelbine, pemetrexed produces equivalent responses and overall survival outcomes, suggesting it is a viable option in NSCLC treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of pemetrexed in non-small cell lung cancer. Longo-Sorbello, GS., Chen, B., Budak-Alpdogan, T., et al.[2022]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

In a study of 109 patients with advanced non-squamous non-small cell lung cancer, the combination of pemetrexed and carboplatin followed by pemetrexed maintenance showed similar efficacy in elderly patients (≥70 years) compared to younger patients, with median progression-free survival of 5.2 months for the elderly versus 5.8 months for younger patients.

While elderly patients experienced more frequent grade 3/4 hematologic toxicities, these were manageable through dose adjustments, and non-hematologic toxicities were similar to those seen in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. Nogami, N., Nishio, M., Okamoto, I., et al.[2022]

In a phase II study involving 62 elderly patients (average age 76.4 years) with advanced non-small cell lung cancer (NSCLC), the combination of pemetrexed and carboplatin achieved an objective tumor response rate of 28.6%, indicating its potential efficacy in this population.

The treatment was generally well-tolerated, although neutropenia was the most common severe side effect, affecting over half of the patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): a phase II trial. Gervais, R., Robinet, G., Clément-Duchêne, C., et al.[2015]

In a study of 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

In a phase II study involving 39 patients with completely resected stage II or III non-small cell lung cancer, 92.3% completed four cycles of adjuvant chemotherapy with nedaplatin and irinotecan, indicating high tolerability of this regimen.

The treatment resulted in a median disease-free survival of 49.4 months and a 5-year overall survival rate of 69.8%, suggesting that nedaplatin and irinotecan are effective options for improving outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. Murakami, S., Saito, H., Kondo, T., et al.[2019]

In a phase III study involving 795 patients with extensive disease small-cell lung cancer, the combination of topotecan and cisplatin (TP) demonstrated noninferior overall survival compared to cisplatin and etoposide (PE), with median survival times of 44.9 weeks for TP and 40.9 weeks for PE.

TP showed superior efficacy in terms of overall response rates (55.5% for TP vs. 45.5% for PE) and longer median time to progression (27.4 weeks for TP vs. 24.3 weeks for PE), but it also had a slightly higher incidence of hematologic toxicities, making it unsuitable as a first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. Fink, TH., Huber, RM., Heigener, DF., et al.[2013]

Combination chemotherapy for small cell lung cancer (SCLC) using platin-compounds and podophyllotoxins results in an 80-90% response rate, with median survival ranging from 11 to 17 months, but overall 5-year survival remains low at about 5%.

For non-small cell lung cancer (NSCLC), while new agents like gemcitabine and taxenes show promise in phase II trials with response rates of 42-55%, further large phase III trials are needed to confirm their efficacy and establish treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung cancer. Hansen, HH., Rørth, M.[2007]

References

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

Chemotherapy in metastatic non-small-cell lung cancer. [2022]

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

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]

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

Future directions in non-small-cell lung cancer: a continuing perspective. [2005]

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

Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. [2022]

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

Role of pemetrexed in non-small cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): a phase II trial. [2015]

9. Ireland pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]

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

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. [2019]

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

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. [2013]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Lung cancer. [2007]