Sotorasib for Solid Cancers

Not currently recruiting at 132 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of sotorasib (also known as Lumakras or AMG-510) for adults with advanced cancers that have a specific gene mutation (KRAS p.G12C). Researchers are testing different combinations of sotorasib with other treatments, such as trametinib or chemotherapy, to find the most effective approach. The trial targets individuals whose cancer has this gene mutation and who can take oral medication. The goal is to understand how well these treatments work together and their effects on participants. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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.

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

Research has shown that sotorasib, used alone or with other drugs, generally maintains a manageable safety profile for people with KRAS G12C-mutated cancers. When used by itself, common side effects include diarrhea, muscle pain, nausea, tiredness, liver issues, and cough, affecting at least 20% of patients in some studies.

Combining sotorasib with trametinib and panitumumab revealed no new severe safety issues. The combination with panitumumab alone is also considered safe and well-tolerated.

In combinations with carboplatin, pemetrexed, docetaxel, paclitaxel, and pembrolizumab, studies have not identified new safety concerns. Promising data also indicate that combining sotorasib with RMC-4630 and TNO155 is generally safe, with no severe or life-threatening treatment-related side effects reported.

However, sotorasib combined with afatinib has shown limited responses in patients, and combining it with pembrolizumab or atezolizumab might increase liver-related side effects. The safety of sotorasib with BI 1701963 and AMG 404 is still under investigation, but the drug is generally considered well-tolerated.

Overall, sotorasib and its combinations have been found relatively safe, but some side effects do occur, so monitoring during treatment is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sotorasib for solid cancers because it uniquely targets the KRAS p.G12C mutation, a common mutation in several advanced cancers like non-small cell lung cancer and colorectal cancer. Traditional treatments often involve chemotherapy or immunotherapy, which can have broad effects and significant side effects. Sotorasib specifically binds to the KRAS mutation, potentially offering a more targeted approach with fewer side effects. Additionally, when combined with other drugs like trametinib, panitumumab, or pembrolizumab, sotorasib may enhance the effectiveness of these treatments, offering new hope for patients with these challenging cancers.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that sotorasib holds promise for treating advanced solid tumors with the KRAS p.G12C mutation. One study found that 41% of patients responded to sotorasib, with benefits lasting an average of 12.3 months and delaying cancer progression for about 6.3 months. In this trial, participants may receive sotorasib alone or combined with other treatments. For instance, one trial arm combines sotorasib with panitumumab, which has helped patients with chemotherapy-resistant colorectal cancer live longer without their cancer worsening compared to standard treatments. Another arm examines the combination of sotorasib with RMC-4630, which was found to be safe and effective for patients with the KRAS p.G12C mutation. These findings suggest that sotorasib, whether used alone or with other treatments, could be a potential option for treating cancers with this mutation. ^{3 4 6 7 8}

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 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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Sotorasib

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.

How Is the Trial Designed?

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

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

Approved in United States as Lumakras for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Approved in European Union as Lumakras for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)

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

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, 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 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 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]

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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04185883

Study Details | NCT04185883 | Sotorasib Activity in ... To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid ...

2. amgen.com amgen.com/newsroom/press-releases/2021/09/lumakras-sotorasib-combined-with-vectibix-panitumumab-showed-encouraging-efficacy-and-safety-in-patients-with-kras-g12cmutated-colorectal-cancer

LUMAKRAS™ (Sotorasib) Combined With Vectibix® ... LUMAKRAS (Sotorasib) combined with Vectibix (Panitumumab) showed encouraging efficacy and safety in patients with KRAS G12C-mutated colorectal cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03600883

NCT03600883 | A Phase 1/2, Study Evaluating the Safety, ... Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10625227/

The current landscape of using direct inhibitors to target ... This review discusses the varying mechanisms of resistance that limit long-lasting effective treatment of those direct inhibitors and highlights several novel ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/214665Orig1s000MultidisciplineR.pdf

214665Orig1s000 - accessdata.fda.gov 357 patients with KRAS G12C mutated solid tumors who received at least one dose of sotorasib. 960mg. The primary safety population consisted ...

6. msds.amgen.com msds.amgen.com/lumakras-safety-datasheet

LUMAKRAS® Sotorasib has been classified per Amgen's Hazard. Classification System as an Occupational Exposure Band 3 compound (20 µg/m3 - 100. µg/m3). Engineering ...

7. lumakrashcp.com lumakrashcp.com/sotorasib-safety

Safety & Adverse Reactions | LUMAKRAS® (sotorasib) The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough in CodeBreaK 100 (N=204).

8. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=20427&isClinicalTrial=True

ANZCTR - Registration G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer. Experimental: Sotorasib + AMG 404 - Experimental: Sotorasib + AMG 404 Dose ...