Sotorasib for Solid Cancers

Recruiting at 103 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Amgen

Disqualifiers: Primary brain tumor, spinal cord compression, myocardial infarction, others

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called sotorasib. It is aimed at adults who have advanced solid tumors with a specific genetic mutation known as KRAS p.G12C. Sotorasib works by blocking this mutation, which can help slow down or stop the growth of the cancer. Sotorasib is the first targeted agent approved for this specific mutation in patients who have previously received treatment.

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 Sotorasib for solid cancers?

Sotorasib has shown promising results in treating non-small cell lung cancer (NSCLC) with KRAS G12C mutations, with a significant number of patients responding to the treatment and experiencing a median progression-free survival of almost 7 months. It has been approved for use in patients with this specific mutation who have already tried other treatments. ^{1 2 3 4 5}

Is sotorasib safe for humans?

Sotorasib has been shown to have a manageable safety profile in clinical trials, with common side effects including diarrhea, muscle pain, nausea, fatigue, liver issues, and cough. It is important to discuss potential risks and benefits with a healthcare provider. ^{1 2 3 6 7}

What makes the drug Sotorasib unique for treating solid cancers?

Sotorasib is unique because it is the first drug specifically targeting the KRAS G12C mutation, which is common in certain solid tumors like non-small cell lung cancer. It works by binding irreversibly to the mutated protein, blocking signals that promote cancer cell growth, and is taken orally, making it more convenient than some other treatments. ^{1 2 3 8 9}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors that have a specific mutation called KRAS p.G12C. Participants must have their condition confirmed by certain lab tests. People with primary brain tumors, recent heart attacks, or issues that prevent taking oral meds can't join.

Inclusion Criteria

My cancer is advanced or has spread, and tests show a KRAS mutation.

I am 18 years old or older.

Exclusion Criteria

I have a primary brain tumor.

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

I do not have active brain issues related to my cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants receive sotorasib in combination with other therapies to determine the optimal dose

12 months

Dose Expansion

Participants continue to receive the determined dose to further evaluate safety and efficacy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Sotorasib (Small Molecule)

Trial Overview The trial is testing the safety of sotorasib in combination with various cancer treatments like chemotherapy and targeted drugs (atezolizumab, carboplatin, etc.) in patients with a particular genetic change in their tumor cells.

Participant Groups

Group I: Sotorasib Monotherapy Experimental Treatment 1 Intervention

Experimental: Sotorasib only Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.

Group II: Sotorasib + trametinib + panitumumab Experimental Treatment 3 Interventions

Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Group III: Sotorasib + pembrolizumab Experimental Treatment 2 Interventions

Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.

Group IV: Sotorasib + panitumumab +/- chemotherapy Experimental Treatment 3 Interventions

Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Group V: Sotorasib + palbociclib Experimental Treatment 2 Interventions

Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Group VI: Sotorasib + everolimus Experimental Treatment 2 Interventions

Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Group VII: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Experimental Treatment 3 Interventions

Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Group VIII: Sotorasib + atezolizumab Experimental Treatment 2 Interventions

Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Group IX: Sotorasib + afatinib Experimental Treatment 2 Interventions

Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Group X: Sotorasib + TNO155 Experimental Treatment 2 Interventions

Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Group XI: Sotorasib + RMC-4630 Experimental Treatment 2 Interventions

Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.

Group XII: Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy Experimental Treatment 4 Interventions

Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.

Group XIII: Sotorasib + BI 1701963 Experimental Treatment 2 Interventions

Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.

Group XIV: Sotorasib + AMG 404 Experimental Treatment 2 Interventions

Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors

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

Sotorasib (LUMAKRAS™) is an innovative treatment specifically targeting KRAS G12C mutations in solid tumors, particularly effective for non-small cell lung cancer (NSCLC) and colorectal cancer.

In May 2021, sotorasib received accelerated approval from the US FDA for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have undergone at least one prior treatment, marking a significant milestone in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: First Approval. Blair, HA.[2022]

In a phase 2 trial involving 126 patients with KRAS p.G12C-mutated advanced non-small-cell lung cancer (NSCLC), sotorasib demonstrated a 37.1% objective response rate, including complete responses in 3.2% of patients, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 12.5 months and a median progression-free survival of 6.8 months, with manageable safety profiles, as 69.8% of patients experienced treatment-related adverse events, mostly of grade 3 severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. Skoulidis, F., Li, BT., Dy, GK., et al.[2022]

Sotorasib is a first-in-class oral medication that specifically targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC), showing a clinically relevant objective response rate in patients during the CodeBreaK 100 trial.

The drug has a manageable safety profile, allowing for dose adjustments to handle any side effects, making it a valuable treatment option for patients with advanced KRAS G12C mutation-positive NSCLC who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. Lee, A.[2022]

Sotorasib is the first commercially available KRASG12C inhibitor, showing promise in improving outcomes for patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), which is prevalent among smokers.

Despite its potential, there are ongoing questions about sotorasib's effectiveness in the brain, optimal dosing, and how it compares to standard treatments, highlighting the need for further research on resistance mechanisms and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Strohbehn, GW., Sankar, K., Qin, A., et al.[2022]

In the phase II CodeBreak 100 trial, the KRASG12C inhibitor sotorasib showed promising efficacy, with over one-third of patients with non-small cell lung cancer responding to the treatment.

Patients treated with sotorasib experienced a median progression-free survival of nearly 7 months, supporting its potential as a significant therapeutic option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Edges Closer to Approval. [2021]

Sotorasib (Lumakras) received accelerated FDA approval for treating advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, showing an overall response rate of 36% in a study of 124 patients.

The median duration of response to sotorasib was 10 months, with common side effects including diarrhea, musculoskeletal pain, and nausea, highlighting its efficacy and safety profile as a targeted therapy for this specific cancer mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. Nakajima, EC., Drezner, N., Li, X., et al.[2022]

Sotorasib and adagrasib, both KRAS G12C-targeting agents, have shown promising efficacy in treating non-small cell lung cancer (NSCLC), with sotorasib achieving an overall response rate of 41% and a progression-free survival of 6.3 months, while adagrasib had an overall response rate of 42.9% and a progression-free survival of 6.5 months.

Both drugs have received accelerated FDA approval and are now recommended as second-line treatment options for patients with KRAS G12C-mutated NSCLC, although they come with common side effects like diarrhea and fatigue, highlighting the need for further studies to refine their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. Mausey, N., Halford, Z.[2023]

Sotorasib, a KRASG12C inhibitor approved for treating advanced KRASG12C-mutated non-small cell lung cancer (NSCLC), has shown promising results in a patient with untreated brain metastases, leading to a complete resolution of neurological symptoms.

This case suggests that sotorasib may have intracranial activity, but further studies are necessary to better understand its effectiveness and response duration in patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report. Yeh, J., Marks, JA., Alzeer, AH., et al.[2022]

Sotorasib, used as a third-line therapy, showed significant efficacy in a patient with KRAS G12C-mutated lung cancer, improving performance status and reversing disseminated intravascular coagulation (DIC) within two weeks.

The treatment led to the disappearance of multiple brain metastases, suggesting that sotorasib may be a viable option for patients with poor performance status and active brain metastases, although the benefits were temporary due to the emergence of new liver metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. Kunimasa, K., Tamiya, M., Inoue, T., et al.[2023]

References

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

Sotorasib: First Approval. [2022]

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

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]

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

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. [2022]

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

Sotorasib Edges Closer to Approval. [2021]

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

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. [2022]

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

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. [2023]

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

Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report. [2022]

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

Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. [2023]