ABP 234 vs Keytruda for Lung Cancer

Recruiting at 185 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: Small cell lung cancer, CNS metastases, Immune-mediated disorders, 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: Unknown

Duration: 49 weeks

927 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to compare the efficacy of ABP 234 with the pembrolizumab reference product (Keytruda®).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had prior systemic treatment for advanced disease.

What data supports the effectiveness of the drug ABP 234 vs Keytruda for lung cancer?

Research shows that pembrolizumab (Keytruda), a part of the treatment being studied, has been effective in treating non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 pathway, which helps the immune system fight cancer. It has shown positive results in both early-phase trials and as a second-line treatment for PD-L1-positive NSCLC. ^{1 2 3 4 5}

Is pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (Keytruda) has been used in various clinical trials and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related reactions such as pneumonitis (lung inflammation), colitis (colon inflammation), and thyroid disorders. These side effects are important to consider when evaluating its safety. ^{3 4 6 7 8}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults with stage IV non-squamous Non-Small Cell Lung Cancer (NSCLC) who haven't had systemic treatment for advanced disease. They should be relatively healthy, able to perform daily activities (ECOG score 0 or 1), and not have certain gene mutations (EGFR, ALK, ROS-1 negative). Participants must also have a life expectancy of at least 3 months and available tumor tissue for testing.

Inclusion Criteria

My lung cancer is advanced and not squamous type.

I have not received any systemic treatment for my advanced disease.

My cancer can be measured by standard health scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or ABP 234 followed by pemetrexed with or without platinum-based chemotherapy

49 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ABP 234
• Pembrolizumab

Trial Overview The study aims to compare the effectiveness of ABP 234 with Keytruda® (pembrolizumab), which are both treatments for lung cancer. Patients will receive either ABP 234 or pembrolizumab to see how well they work in treating their cancer.

Participant Groups

Group I: Pembrolizumab (US) Experimental Treatment 1 Intervention

Part 1: Participants will receive FDA-licensed pembrolizumab followed by pemetrexed administered with platinum-based chemotherapy (cisplatin or carboplatin). Part 2: Participants will receive FDA-licensed pembrolizumab followed by pemetrexed.

Group II: Pembrolizumab (EU) Experimental Treatment 1 Intervention

Part 1: Participants will receive EU-approved pembrolizumab followed by pemetrexed administered with platinum-based chemotherapy (cisplatin or carboplatin). Part 2: Participants will receive EU-approved pembrolizumab followed by pemetrexed.

Group III: ABP 234 Experimental Treatment 1 Intervention

Part 1: Participants will receive ABP 234 followed by pemetrexed administered with platinum-based chemotherapy (cisplatin or carboplatin). Part 2: Participants will receive ABP 234 followed by pemetrexed.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

In a study of 411 patients with non-small cell lung cancer (NSCLC), 33% showed no PD-L1 expression, 38% had low expression, and 29% exhibited high expression, indicating a significant variability in PD-L1 status among patients.

The study found that PD-L1 positivity was linked to factors such as male sex, smoking history, higher tumor grade, and specific histologic types, suggesting that these characteristics may influence the effectiveness of pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience. Takeda, M., Kasai, T., Naito, M., et al.[2022]

In a study involving 1,453 patients with advanced melanoma and non-small cell lung cancer (NSCLC), pembrolizumab showed no dependency on dosage for overall survival, indicating that varying doses (2 to 10 mg/kg) did not significantly affect patient outcomes.

A strong association was found between the baseline clearance (CL0) of pembrolizumab and overall survival, suggesting that higher clearance rates may indicate more severe disease, rather than affecting the drug's efficacy directly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Exposure-Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance. Turner, DC., Kondic, AG., Anderson, KM., et al.[2019]

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, 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]

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 (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

References

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

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience. [2022]

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

Pembrolizumab Exposure-Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance. [2019]

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. England pubmed.ncbi.nlm.nih.gov

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

5. France pubmed.ncbi.nlm.nih.gov

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

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

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

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]