AMG 510 for Non-Small Cell Lung Cancer

Recruiting at 289 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Disqualifiers: Active brain metastases, recent myocardial infarction, GI tract disease, 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: 24.3 months

345 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 3 Study to Compare AMG 510 with Docetaxel in Non Small Cell Lung Cancer (NSCLC) subjects with KRAS p. G12c mutation

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug AMG 510 for non-small cell lung cancer?

Research shows that docetaxel, a component of the treatment, has been effective in improving survival and quality of life for patients with advanced non-small cell lung cancer, especially in those who have already received other treatments. In several studies, patients treated with docetaxel lived longer and had better outcomes compared to those who received other treatments or supportive care. ^{1 2 3 4 5}

Is docetaxel safe for humans?

Docetaxel, used for various cancers including lung cancer, can cause side effects like severe neutropenia (low white blood cell count) and fluid retention, but these can often be managed with medication. Hypersensitivity reactions (allergic reactions) are also possible, but protocols exist to help manage them. ^{1 2 6 7 8}

What makes the drug AMG 510 unique for treating non-small cell lung cancer?

AMG 510 is unique because it targets a specific mutation in the KRAS gene, which is a common mutation in non-small cell lung cancer, offering a more personalized treatment approach compared to traditional chemotherapy like docetaxel. ^{5 9 10 11 12}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults over 18 with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that has a specific KRAS p.G12C mutation. Participants should have an ECOG performance status of ≤1, indicating they are relatively active. They can't join if they have active brain tumors, recent heart attacks, or GI diseases preventing oral medication intake.

Inclusion Criteria

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

My advanced lung cancer has a specific KRAS mutation.

I am 18 years old or older.

Exclusion Criteria

I cannot take pills due to a stomach or intestine problem.

I have not had a heart attack in the last 6 months.

I have active cancer spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AMG 510 or Docetaxel for the treatment of NSCLC with KRAS p.G12C mutation

24.3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Pharmacokinetics Assessment

Characterization of the pharmacokinetics of AMG 510

4 months

Treatment Details

Interventions

• AMG 510
• Docetaxel

Trial Overview The study compares AMG 510 (Sotorasib), a new treatment option, to Docetaxel, an established chemotherapy drug in patients with NSCLC who carry the KRAS p.G12c mutation and have been previously treated.

Participant Groups

Group I: AMG 510 Experimental Treatment 1 Intervention

Group II: Docetaxel Active Control 1 Intervention

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

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 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]

In two phase III trials involving patients with previously treated non-small cell lung cancer, docetaxel at a dose of 75 mg/m2 significantly improved median survival (7.5 months) compared to best supportive care (4.6 months) and showed a higher 1-year survival rate (37% vs 11%).

Docetaxel at 75 mg/m2 also demonstrated comparable efficacy to other treatments like vinorelbine/ifosfamide, with manageable and predictable adverse events, confirming its role as an effective second-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials. Shepherd, FA., Fossella, FV., Lynch, T., et al.[2019]

In two phase III trials involving patients with previously treated non-small cell lung cancer, docetaxel at a dose of 75 mg/m2 significantly improved median survival (7.5 months) compared to best supportive care (4.6 months) and showed a higher 1-year survival rate (37% vs 11%).

Docetaxel at 75 mg/m2 also demonstrated comparable efficacy to other treatments like vinorelbine/ifosfamide, with manageable and predictable adverse events, confirming its role as an effective second-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: A review of two phase III trials. Shepherd, FA., Fossella, FV., Lynch, T., et al.[2019]

Docetaxel is a highly effective treatment for advanced non-small-cell lung cancer (NSCLC), showing improved patient quality of life compared to vinorelbine-cisplatin in clinical trials, leading to its FDA approval for this indication.

With a higher binding affinity for beta tubulin than paclitaxel, docetaxel is the only chemotherapy agent approved for both first- and second-line therapy of advanced NSCLC, demonstrating its versatility and efficacy in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. Belani, CP., Eckardt, J.[2022]

Docetaxel is an effective chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, S.[2018]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. Kris, MG., Manegold, C.[2019]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. Kris, MG., Manegold, C.[2019]

Docetaxel is recognized as one of the most effective cytotoxic drugs for treating non-small cell lung cancer, with ongoing clinical investigations exploring its use in combination therapies and radiotherapy.

Current studies at our hospital include trials combining docetaxel with gemcitabine and ifosfamide, as well as a planned randomized study to evaluate its effectiveness in conjunction with chemoradiotherapy for patients with inoperable stage III non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in non-small cell lung cancer: ongoing studies in Heidelberg and future plans. Manegold, C.[2022]

References

1. 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]

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

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

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

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials. [2019]

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

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: A review of two phase III trials. [2019]

5. Ireland pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Hypersensitivity reactions to docetaxel: retrospective evaluation and development of a desensitization protocol. [2018]

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

Clinical studies of docetaxel (Taxotere) and concomitant chest therapy. [2018]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. [2019]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. [2019]

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

Docetaxel (Taxotere) in non-small cell lung cancer: ongoing studies in Heidelberg and future plans. [2022]

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

Emerging role of docetaxel (Taxotere) in advanced non-small cell lung cancer. [2018]