Ivonescimab + Pembrolizumab for Lung Cancer

Recruiting at154 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Summit Therapeutics

Disqualifiers: Small cell lung cancer, Genomic alterations, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing two treatments for advanced lung cancer. One uses a new drug, Ivonescimab, and the other uses an existing drug, Pembrolizumab, both combined with chemotherapy. The goal is to see which treatment helps patients live longer and has fewer side effects.

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 any prior therapy for metastatic non-small cell lung cancer.

What data supports the effectiveness of the drug Ivonescimab + Pembrolizumab for lung cancer?

Pembrolizumab, one of the drugs in the combination, has shown promising results in treating non-small cell lung cancer, as it has been effective in patients with advanced stages of this cancer. ^{1 2 3 4 5}

Is the combination of Ivonescimab and Pembrolizumab safe for humans?

Pembrolizumab, one of the drugs in the combination, has been studied in various trials and is generally considered safe, but it can cause side effects like hypothyroidism (low thyroid function), pneumonitis (lung inflammation), and hyperthyroidism (overactive thyroid). There is no specific safety data available for the combination of Ivonescimab and Pembrolizumab, so it's important to discuss potential risks with your doctor. ^{1 3 6 7 8}

What makes the drug combination of Ivonescimab and Pembrolizumab unique for lung cancer treatment?

The combination of Ivonescimab and Pembrolizumab is unique because Ivonescimab is a bi-specific antibody that targets both PD-1 and VEGF, potentially enhancing the immune response against cancer cells while also inhibiting blood vessel growth that tumors need to grow, which is different from standard treatments that typically target only one pathway. ^{1 2 3 4 9}

Research Team

Eligibility Criteria

Adults with metastatic squamous non-small cell lung cancer (NSCLC) who have not had previous treatments for their advanced disease. Participants must have a certain level of PD-L1 expression, be in good physical condition (ECOG score 0 or 1), and expect to live at least three more months. They cannot join if they have small cell lung carcinoma, non-squamous NSCLC, major blood vessel involvement by the tumor, or known specific genetic alterations.

Inclusion Criteria

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

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

You are expected to live for at least 3 more months.

Exclusion Criteria

My lung cancer is confirmed to be either small cell or non-squamous non-small cell.

My cancer has specific genetic changes in EGFR, ALK, or ROS1.

I have received treatment for my lung cancer after it spread.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ivonescimab or pembrolizumab combined with chemotherapy for the first-line treatment of metastatic non-small cell lung cancer

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

approximately 6 years

Treatment Details

Interventions

• Ivonescimab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview This Phase 3 trial is testing Ivonescimab combined with chemotherapy against Pembrolizumab with chemotherapy as first-line treatment options for metastatic squamous NSCLC. The main goal is to see which treatment helps patients live longer without their cancer getting worse.

Participant Groups

Group I: Arm A - Ivonescimab and chemotherapy Experimental Treatment 1 Intervention

Subject will receive ivonescimab and chemotherapy

Group II: Arm B - Pembrolizumab and chemotherapy Active Control 1 Intervention

Subject will receive pembrolizumab and chemotherapy

Ivonescimab is already approved in China for the following indications:

Approved in China as Ivonescimab for:

• Locally advanced or metastatic non-squamous NSCLC

Who Is Running the Clinical Trial?

Summit Therapeutics

Lead Sponsor

Trials

18

Recruited

4,500+

Findings from Research

The phase I study of the OX40 agonistic monoclonal antibody GSK3174998, alone or with pembrolizumab, was well tolerated among 138 patients with advanced solid tumors, with treatment-related adverse events occurring in 51% of patients in Part 1 and 64% in Part 2, but no maximum-tolerated dose was reached.

Despite demonstrating target engagement and some immune response changes in the tumor microenvironment, GSK3174998 showed limited clinical activity, with a disease control rate of only 9% in Part 1 and no significant improvement when combined with pembrolizumab, indicating it may not be viable for further development in advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). Postel-Vinay, S., Lam, VK., Ros, W., et al.[2023]

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 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]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In the JAVELIN Lung 200 trial, avelumab showed improved 2-year overall survival (OS) rates compared to docetaxel in patients with higher PD-L1 expression, with rates of 36.4% for those with ≥50% PD-L1 and 40.2% for those with ≥80% PD-L1, indicating potential efficacy in specific subgroups.

Despite the primary analysis showing no significant overall survival benefit for avelumab compared to docetaxel, the longer follow-up data suggests that avelumab may be more effective for patients with higher PD-L1 expression, with a median duration of response of 19.1 months compared to 5.7 months for docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial. Park, K., Özgüroğlu, M., Vansteenkiste, J., et al.[2021]

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]

In a study of 550 patients with advanced non-small-cell lung cancer, pembrolizumab demonstrated a 41% objective response rate in treatment-naive patients and a 23% response rate in previously treated patients, indicating its efficacy as a treatment option.

The median overall survival was significantly longer for treatment-naive patients (22.3 months) compared to previously treated patients (10.5 months), with safety data showing that only 12% experienced grade 3-5 treatment-related adverse events, suggesting a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Leighl, NB., Hellmann, MD., Hui, R., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). [2023]

2. France pubmed.ncbi.nlm.nih.gov

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

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

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

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