EIK1001 + Pembrolizumab and Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 38 trial locations

Overseen By Surya Vangala

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eikon Therapeutics

Disqualifiers: Small cell elements, Prior malignancy, Active infection, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

70 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 should not have received prior systemic treatment for advanced/metastatic NSCLC.

What data supports the effectiveness of the drug EIK1001 + Pembrolizumab and Chemotherapy for Non-Small Cell Lung Cancer?

Research shows that pembrolizumab, a part of this drug combination, has been effective in treating non-small cell lung cancer, offering significant survival benefits and long-lasting responses. It is especially effective in patients with high levels of PD-L1, a protein that helps cancer cells hide from the immune system. ^{1 2 3 4 5}

Is the combination of EIK1001 and pembrolizumab safe for humans?

Pembrolizumab, when used alone or with chemotherapy for non-small cell lung cancer, generally has a favorable safety profile, with less than 10% of patients experiencing serious immune-related side effects. These side effects are often reversible with proper management. ^{6 7 8 9 10}

What makes the drug EIK1001 unique for treating non-small cell lung cancer?

EIK1001 is unique because it is being tested in combination with pembrolizumab and chemotherapy, which may offer a new approach to enhance the immune system's ability to fight non-small cell lung cancer. This combination could potentially improve treatment outcomes compared to using pembrolizumab or chemotherapy alone. ^{1 4 11 12 13}

What is the purpose of this trial?

This study is for patients with advanced/metastatic non-small cells lung cancer (NSCLC) who have not received any treatment through the vein for the advanced disease.

Research Team

Wale Akinseli, MD, MPH

Principal Investigator

Eikon Therapeutics

Etah Kurland, MD

Principal Investigator

Eikon Therapeutics

Eligibility Criteria

This trial is for adults with advanced stage 4 non-small cell lung cancer who haven't had intravenous treatment for their condition. Specific eligibility details are not provided, but typically participants need to meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

My organs are functioning well.

I haven't had systemic treatment for advanced lung cancer.

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

Exclusion Criteria

Is currently participating in or has participated in a study of an investigational agent and received investigational therapy within 4 weeks or 5 half-lives (whichever is shorter) of administration of EIK1001

My lung cancer is not mainly squamous or non-squamous cell type.

I have had treatment or major surgery for my cancer less than 3 weeks before starting EIK1001.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EIK1001 in combination with Pembrolizumab and Chemotherapy

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Treatment Details

Interventions

• EIK1001

Trial Overview The study tests a combination of EIK1001 with the immunotherapy drug Pembrolizumab and chemotherapy drugs Paclitaxel, Pemetrexed, and Carboplatin. It's likely that patients will be randomly assigned to receive either this combination or a standard treatment as part of the research.

Participant Groups

Group I: Cohort B - Participants with squamous NSCLC Experimental Treatment 4 Interventions

Participants in this arm will receive EIK1001 + Standard of Care (SOC).

Group II: Cohort A - Participants with non-squamous NSCLC Experimental Treatment 4 Interventions

Participants in this arm will receive EIK1001 + Standard of Care (SOC).

Who Is Running the Clinical Trial?

Eikon Therapeutics

Lead Sponsor

Trials

8

Recruited

1,300+

Findings from Research

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]

In a study of 566 patients with metastatic non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab, the median overall survival was 19.6 months, with 3-year survival rates of 36.2%, indicating promising long-term outcomes in a real-world setting.

The study found that 38.6% of patients experienced a real-world tumor response, with the most common reasons for discontinuation of treatment being disease progression and therapy-related adverse effects, highlighting the treatment's efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Outcomes of First-Line Pembrolizumab Monotherapy for Metastatic Non-Small Cell Lung Cancer With ≥50% Expression of Programmed Cell Death-Ligand 1. Velcheti, V., Hu, X., Yang, L., 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 study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

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]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a study of patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab, a higher overall tumor burden was associated with a lower incidence of severe immune-related adverse events (irAEs), suggesting that tumor size may influence treatment safety.

Good performance status and high PD-L1 expression were significant predictors of developing severe irAEs, with odds ratios of 3.27 and 4.44, respectively, indicating that patients with these characteristics should be closely monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. Sumi, T., Koshshino, Y., Sekikawa, M., et al.[2022]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor for non-small cell lung cancer (NSCLC), has a favorable safety profile, with serious immune-related adverse events occurring in less than 10% of patients when used alone.

Monotherapy with pembrolizumab not only improves health-related quality of life compared to chemotherapy but also allows for effective management of immune-related adverse events, which are often reversible with proper treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of pembrolizumab for the treatment of non-small cell lung cancer. Mazarico Gallego, JM., Herrera Juárez, M., Paz-Ares, L.[2020]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

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, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Outcomes of First-Line Pembrolizumab Monotherapy for Metastatic Non-Small Cell Lung Cancer With ≥50% Expression of Programmed Cell Death-Ligand 1. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

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

Pembrolizumab. [2022]

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

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of pembrolizumab for the treatment of non-small cell lung cancer. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

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

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. [2020]