Sotorasib Combo vs Pembrolizumab Combo for Advanced Lung Cancer

Recruiting in Palo Alto (17 mi)

+376 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Amgen

Disqualifiers: Mixed histology NSCLC, Brain metastases, GI tract disease, Myocardial infarction, 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 different drug combinations with chemotherapy to see which helps cancer patients live longer without their disease getting worse. One combination includes sotorasib, which targets cancer mutations, and the other includes pembrolizumab, which helps the immune system fight cancer. Pembrolizumab has been shown to improve overall survival in various cancers when combined with chemotherapy.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug pembrolizumab in treating advanced lung cancer?

Research shows that pembrolizumab significantly improves survival in patients with advanced non-small-cell lung cancer (NSCLC) compared to traditional chemotherapy, especially in those with high levels of a protein called PD-L1. This suggests that pembrolizumab can be an effective treatment option for this type of lung cancer.

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Is the combination of Sotorasib and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied in various trials for lung cancer and has shown a safety profile with fewer treatment-related side effects compared to traditional chemotherapy. While specific safety data for the combination with Sotorasib is not provided, Pembrolizumab alone has been generally safe in humans.

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How is the Sotorasib and Pembrolizumab drug combination unique for advanced lung cancer?

The Sotorasib and Pembrolizumab combination is unique because it combines Sotorasib, a targeted therapy that specifically inhibits a mutation in the KRAS gene, with Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells. This combination targets both the genetic mutation and enhances the immune response, offering a novel approach compared to standard chemotherapy or immunotherapy alone.

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Eligibility Criteria

This trial is for adults with advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that has a specific mutation (KRAS p. G12C) and no PD-L1 expression. They should not have had cancer treatment in the metastatic setting, be relatively fit (ECOG ≤ 1), and able to take oral medication.

Inclusion Criteria

I haven't had any systemic anticancer therapy for incurable cancer.

My advanced lung cancer is KRAS G12C mutation positive and PD-L1 negative.

I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

I have brain metastases that cause symptoms.

My lung cancer is mixed type with specific cell features.

I have been treated with a KRAS G12C inhibitor before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sotorasib with platinum doublet chemotherapy or pembrolizumab with platinum doublet chemotherapy

Approximately 5.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study compares two treatments: Sotorasib with platinum chemotherapy versus Pembrolizumab with the same chemo, focusing on how long patients live without their cancer getting worse.

Group I: Sotorasib combined with carboplatin and pemetrexed Experimental Treatment 1 Intervention

Sotorasib administered in combination with carboplatin and pemetrexed.

Group II: Pembrolizumab combined with carboplatin and pemetrexed Active Control 1 Intervention

Pembrolizumab administered in combination with carboplatin and pemetrexed.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸 Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

🇪🇺 Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

🇬🇧 Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Norton Cancer Institute - Brownsboro Louisville, KY

University of Pittsburgh Medical Center Hillman Cancer Center Pittsburgh, PA

Queen Elizabeth II, Health Sciences Centre Halifax, Canada

Allan Blair Cancer Centre Regina, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Amgen Lead Sponsor

References

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022] In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.

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

Current uses of check inhibitors in the fight against advanced and/or metastatic lung cancer: will immunotherapy overcome chemotherapy? [2020] Lung cancer is the most common cause of cancer death worldwide. Treatment for lung cancer has become increasingly more complex over the last several years. Immune checkpoint inhibitors have dramatically changed the treatment landscape of advanced nonsmall cell lung cancer (NSCLC). There are currently 3 approved checkpoint inhibitors for patients with NSCLC who progressed after platinum-doublet chemotherapy (Pembrolizumab and /or Nivolumab and /or Atezolizumab). Avelumab and durvalumab are currently under investigation in phase 3 trials. Pembrolizumab has now been approved for first-line use in NSCLC, after a trial showed improved survival compared with chemotherapy in patients who were positive for programmed cell death ligand 1. Giving our patients the best, personalized approach to their individual cancer can improve their quality of life and survival and help us use our limited resources most efficiently. In the present review, we provide a new patient-oriented algorithm to guide clinicians' decisions on the best choice of therapy for advanced NSCLC.

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] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

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

First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50. [2021] Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer without EGFR mutations or ALK rearrangements, regardless of PD-L1 expression status. A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with PD-L1 ≥50%. The aim of this trial is to perform such a comparison as first-line treatment in patients not eligible for locally advanced treatment who have expression of PD-L1 on ≥50% of tumor cells. The expected results are a reduction in the risk of early progression. A higher objective tumor response is also expected with the combination of chemotherapy and pembrolizumab compared with pembrolizumab alone. The study will allow a direct comparison of the proportion of patients who derive long-term benefit from the treatment. Clinical trial number: EudraCT (2020-002626-86); ClinicalTrials.gov (NCT04547504).

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

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. [2022] Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.

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

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. [2021] The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions.

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

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

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. [2022] Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis.

9. New Zealand pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. [2020] Pembrolizumab monotherapy showed significantly longer overall survival and fewer treatment-related adverse events compared to chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1)-positive tumors in the first-line setting in KEYNOTE (KN)-024 and in those previously treated in KN010. The objective of this analysis was to assess the benefit-risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials.

10. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023] Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.

11. Singapore pubmed.ncbi.nlm.nih.gov

Two-year efficacy of SNK01 plus pembrolizumab for non-small cell lung cancer: Expanded observations from a phase I/IIa randomized controlled trial. [2022] A previous trial showed that autologous ex-vivo expanded NK cell (SNK01) treatment combined with pembrolizumab showed better efficacy than pembrolizumab monotherapy in advanced non-small cell lung cancer (NSCLC). This study was a 2-year follow-up of that previous study to determine the long-term efficacy of the combination treatment.

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

Combo Therapy for Lung Cancer Extends Survival. [2019] The PD-1 inhibitor pembrolizumab in combination with chemotherapy may be an effective therapy for patients with newly diagnosed advanced non-squamous non-small cell lung cancer. In a clinical trial, patients who received the combination had an estimated 12-month overall survival rate of 69.2%, compared with 49.4% in patients who received chemotherapy alone.