MK-2870 for Non-Small Cell Lung Cancer

Recruiting at 194 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: EGFR TKIs

Must not be taking: Immunosuppressants, Corticosteroids

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: 1

Duration: Up to approximately 41 months

556 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate sacituzumab tirumotecan versus chemotherapy (docetaxel or pemetrexed) for the treatment of previously-treated non-small cell lung cancer (NSCLC) with exon 19del or exon 21 L858R EGFR mutations (hereafter referred to as EGFR mutations or EGFR-mutated) or any of the follow genomic alterations: ALK gene rearrangements, ROS1 rearrangements, BRAF V600E mutations, NTRK gene fusions, MET exon 14 skipping mutations, RET rearrangements, or less common EGFR point mutations of exon 20 S768I, exon 21 L861Q, or exon 18 G719X mutations. The primary hypotheses are that sacituzumab tirumotecan is: (1) superior to chemotherapy with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR in NSCLC with EGFR mutations; and (2) superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received any systemic anticancer therapy, including investigational agents, within 4 weeks before joining the study.

What data supports the effectiveness of the drug MK-2870 for treating non-small cell lung cancer?

Research shows that docetaxel and pemetrexed, which are part of the treatment, have been used effectively in treating non-small cell lung cancer. Docetaxel has shown a survival benefit in various cancer settings, and pemetrexed has been approved for use in non-small cell lung cancer with a favorable safety profile. ^{1 2 3 4 5}

What safety data exists for MK-2870 and related treatments in humans?

Docetaxel and pemetrexed, which are related to MK-2870, have been studied for safety in treating non-small cell lung cancer. Pemetrexed is considered to have a more favorable safety profile than docetaxel, causing fewer issues like low white blood cell counts and related infections. ^{2 4 5 6 7}

What makes the drug MK-2870 unique for treating non-small cell lung cancer?

The drug MK-2870, when combined with docetaxel and pemetrexed, offers a novel approach by potentially enhancing the effectiveness of existing chemotherapy agents like docetaxel and pemetrexed, which have shown significant activity against non-small cell lung cancer. This combination may provide a new option for patients who have progressed on or after standard treatments. ^{8 9 10 11 12}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced or metastatic non-squamous NSCLC who have specific mutations and have already tried some treatments. They should be relatively healthy (ECOG status of 0 or 1), not have certain infections, and must not have had recent vaccinations or other cancer treatments within the last month.

Inclusion Criteria

My advanced lung cancer is non-squamous and has specific mutations.

My cancer has grown despite treatment, as shown by scans.

I've had specific lung cancer treatments, including a targeted therapy for a certain mutation.

Exclusion Criteria

Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

I experience significant numbness or pain in my hands or feet.

I have severe dry eye, eyelid inflammation, or corneal disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab tirumotecan or chemotherapy (docetaxel or pemetrexed) in 6-week cycles

Up to approximately 41 months

IV infusions on Days 1, 15, and 29 for sacituzumab tirumotecan; Days 1 and 22 for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

Treatment Details

Interventions

• Docetaxel
• MK-2870
• Pemetrexed

Trial Overview The study tests MK-2870 against standard chemotherapy drugs (docetaxel or pemetrexed) in patients with certain genetic changes in their lung cancer. The goal is to see if MK-2870 can improve survival without the disease getting worse compared to chemotherapy.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 1 Intervention

Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle. 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: Chemotherapy Active Control 2 Interventions

Participants will receive 75 mg/m\^2 of docetaxel or 500 mg/m\^2 of pemetrexed by IV infusion on Days 1 and 22 of every 6-week cycle.

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate 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

In a study of 148 patients with nonsquamous non-small-cell lung cancer, the progression-free survival (PFS) and response rates were similar for both pemetrexed plus cisplatin (Pem-Cis) and docetaxel plus cisplatin (Doc-Cis) regimens, indicating that both treatments are comparably effective.

However, docetaxel plus cisplatin was associated with a longer median overall survival (13.3 months) compared to pemetrexed plus cisplatin (11.7 months), but this difference was not statistically significant, and the Doc-Cis regimen had a higher incidence of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. Park, CK., Oh, IJ., Kim, KS., et al.[2018]

In a study of 170 patients with advanced non-small cell lung cancer, those treated with EGFR-TKIs as second-line therapy showed the highest response rate (36.1%) and the longest progression-free survival (PFS) of 9.31 months, compared to 15.0% response rate and 5.49 months PFS for docetaxel and 24.5% response rate and 5.42 months PFS for pemetrexed.

All three treatments (docetaxel, pemetrexed, and EGFR-TKIs) had comparable safety profiles, but there was no significant difference in median survival time (MST) among the groups, indicating that while EGFR-TKIs may offer better short-term benefits, long-term survival outcomes were similar across treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer]. Zhang, RX., Cai, DY., Wu, XH., et al.[2018]

Docetaxel has shown impressive efficacy in treating various cancers, including breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer, outperforming or matching established chemotherapy regimens in phase III trials involving multiple tumor types.

In addition to its effectiveness, docetaxel is often associated with an improved safety profile, and it has demonstrated a survival benefit in previously challenging cases, such as anthracycline-resistant breast cancer and second-line NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. Hong, WK.[2018]

Pemetrexed was approved for treating advanced non-small cell lung cancer based on a trial with 571 patients, showing median survival times of 8.3 months compared to 7.9 months for docetaxel, although neither drug was proven superior.

Pemetrexed demonstrated a better safety profile than docetaxel, causing significantly less neutropenia and related complications, making it a potentially safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. Cohen, MH., Johnson, JR., Wang, YC., et al.[2022]

In a randomized Phase 2 trial comparing pemetrexed and docetaxel in patients with nonsmall-cell lung cancer (NSCLC) after failing EGFR-TKI therapy, both treatments showed similar effectiveness in terms of disease control and survival rates.

Pemetrexed was associated with significantly fewer adverse effects, such as nausea and myelosuppression, making it a better-tolerated option for salvage chemotherapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pemetrexed and docetaxel as salvage chemotherapy for the treatment for nonsmall-cell lung cancer after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors. Dong, L., Han, ZF., Feng, ZH., et al.[2022]

In a phase II study involving 44 patients with advanced non-small-cell lung cancer resistant to platinum chemotherapy, docetaxel showed a 21% partial response rate, indicating its efficacy in this challenging patient population.

The treatment was associated with significant side effects, particularly grade 3/4 neutropenia in 85% of patients, along with hypersensitivity reactions and fluid retention, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. Fossella, FV., Lee, JS., Shin, DM., et al.[2018]

In a phase II study involving 41 chemotherapy-naive patients with advanced non-small-cell lung cancer, docetaxel showed significant efficacy, achieving a 33% partial response rate with a median response duration of 14 weeks.

The treatment was associated with notable toxicities, including severe neutropenia in 97% of patients, hypersensitivity reactions in 36%, and fluid retention in 54%, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. Fossella, FV., Lee, JS., Murphy, WK., et al.[2018]

Docetaxel (Taxotere) has been shown to significantly improve survival and symptom control in patients with non-small cell lung cancer compared to best supportive care, as demonstrated in the TAX 317 trial.

Pemetrexed (Alimta) has similar response and survival rates to docetaxel but has a better safety profile, causing less severe neutropenia and requiring fewer hospitalizations, making it a preferable option for second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy for non-small cell lung cancer. Shepherd, FA.[2022]

Docetaxel shows significant efficacy in treating advanced non-small cell lung cancer, with a 30% partial response rate in chemotherapy-naive patients and 20% in those who had previously failed platinum-based treatments, based on six phase II studies involving 268 patients.

The primary side effect of docetaxel is neutropenia, while fluid retention is common but usually manageable with corticosteroids, indicating that the treatment has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. Fossella, FV., Lee, JS., Berille, J., et al.[2018]

In a study using three human lung cancer cell lines, simultaneous treatment with pemetrexed and docetaxel showed antagonistic effects, suggesting that this combination may not be effective when given at the same time.

However, administering pemetrexed followed by docetaxel resulted in synergistic effects in two of the cell lines, indicating that this sequential approach could enhance anti-tumor efficacy in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedule-dependent synergism and antagonism between pemetrexed and docetaxel in human lung cancer cell lines in vitro. Kano, Y., Tanaka, M., Akutsu, M., et al.[2018]

Ramucirumab, when combined with docetaxel, improves overall survival by 1.4 months for patients with metastatic non-small cell lung cancer (NSCLC) who have progressed after platinum-based chemotherapy.

The treatment has an acceptable safety profile, but its role may be influenced by the introduction of PD-1-blocking antibodies like nivolumab or pembrolizumab in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. Takeda, K., Daga, H.[2023]

Lung cancer is the leading cause of cancer-related deaths in Europe and North America, with non-small cell lung cancer (NSCLC) making up 70-80% of cases, and current chemotherapy treatments show limited effectiveness with overall response rates below 20%.

The Southern Italy Cooperative Oncology Group is exploring new triplet chemotherapy combinations involving cisplatin and two additional agents, aiming to improve patient outcomes in advanced NSCLC, with ongoing phase I, II, and III trials evaluating the safety and efficacy of these new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. Frasci, G., Panza, N., Comella, G., et al.[2022]

References

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

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. [2018]

2. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer]. [2018]

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

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. [2018]

4. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. [2022]

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

Comparison of pemetrexed and docetaxel as salvage chemotherapy for the treatment for nonsmall-cell lung cancer after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors. [2022]

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

Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. [2018]

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

Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy for non-small cell lung cancer. [2022]

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

Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Schedule-dependent synergism and antagonism between pemetrexed and docetaxel in human lung cancer cell lines in vitro. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. [2022]