AMG 510 for Non-Small Cell Lung Cancer

Not currently recruiting at 370 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, AMG 510, against the standard treatment, Docetaxel, for individuals with Non-Small Cell Lung Cancer (NSCLC). The focus is on patients whose cancer has a KRAS p.G12C mutation, a specific genetic change in the cancer cells. The trial aims to determine if AMG 510 is more effective than the usual treatment. Individuals diagnosed with this mutation in their NSCLC who have already tried other treatments might be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AMG 510 is generally well tolerated by patients with advanced non-small cell lung cancer (NSCLC) who have a specific genetic mutation called KRAS G12C. In various studies, patients did not experience serious side effects that would prevent dose increases. Many patients maintained stable disease, meaning their cancer did not worsen.

The FDA has already approved AMG 510 for another use, indicating its safety is well understood. During trials, most side effects were mild and manageable, supporting the idea that AMG 510 is safe for people.

In the trial for AMG 510, researchers use another drug, Docetaxel, for comparison. Docetaxel is a standard chemotherapy drug with known side effects, such as tiredness and nausea. When considering joining a clinical trial, it's important to weigh these factors and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

AMG 510 is unique because it targets a specific mutation in the KRAS gene, known as KRAS G12C, which is involved in the growth of non-small cell lung cancer cells. This mutation-specific action sets it apart from standard chemotherapy treatments like Docetaxel, which don't target specific genetic mutations. Researchers are excited about AMG 510 because it represents a precision medicine approach, potentially offering more effective and personalized treatment for patients with this specific genetic profile, and it could lead to improved outcomes compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that AMG 510, a treatment under study in this trial, may help treat non-small cell lung cancer (NSCLC) with a specific KRAS mutation. In one study, about 37% of patients with this mutation saw their tumors shrink or disappear. Another study found that when combined with chemotherapy, AMG 510 led to tumor shrinkage in about 65% of patients. These findings suggest that AMG 510, especially when combined with other treatments, can effectively reduce tumors in people with this type of lung cancer. Research also indicates that AMG 510 is generally well tolerated, meaning most people do not experience severe side effects. Participants in this trial will receive either AMG 510 or Docetaxel, another treatment option under study. ^{1 2 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12037499/

Current status of KRAS G12C inhibitors in NSCLC and the ...

In the CodeBreaK 101 trial, AMG 510 combined with platinum-doublet chemotherapy showed notable results in NSCLC patients, with a 65% ORR, a ...

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jto.org

jto.org/article/S1556-0864(19)33348-9/fulltext

OA01.06 Safety, Efficacy, and Pharmacokinetics of AMG ...

AMG 510 is well tolerated at all 4 dose levels and shows antitumor activity when administered as monotherapy to patients with advanced KRASG12C mutant NSCLC.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04625647

Study Details | NCT04625647 | Testing the Use of Targeted ...

This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back ...

4.

nature.com

nature.com/articles/s41698-021-00237-5

Selective KRAS G12C inhibitors in non-small cell lung ...

Phase II data for sotorasib (AMG510) has demonstrated a 37.1% overall response rate (ORR). Adagrasib (MRTX849) has demonstrated a 45% ORR in an ...

5.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)58668-9/fulltext

Phase I study of AMG 510, a novel molecule targeting ...

AMG 510 is well tolerated with no DLTs at studied doses. Early results suggest antitumor activity of single-agent AMG 510 in pts with KRASG12C mutant solid ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04933695

NCT04933695 | A Study of Sotorasib (AMG 510) in ...

A Phase 2, Multicenter, Open-label Study of Sotorasib (AMG 510) in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-line ...

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aacrjournals.org

aacrjournals.org/cancerdiscovery/article/10/8/1084/2709/AMG-510-Shows-Activity-beyond-NSCLCAMG-510-Shows

AMG 510 Shows Activity beyond NSCLC - AACR Journals

Among 42 evaluable patients, three responded partially to AMG 510—all of whom received the highest dose, 960 mg—and another 29 saw their disease stabilize. The ...