Sotorasib for Solid Tumors

Recruiting at 141 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Amgen

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

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

Compensation: Varies

Number of Visits: Unknown

713 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether 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 (AMG 510) for solid tumors?

Sotorasib has shown promising results in treating non-small cell lung cancer (NSCLC) with a specific KRAS mutation, leading to its approval for this condition. In clinical trials, it helped shrink tumors in patients with this mutation, suggesting it may be effective for other solid tumors with similar genetic profiles. ^{1 2 3 4 5}

Is sotorasib safe for humans?

Sotorasib has been studied for safety, showing no major safety concerns in nonclinical studies, but it can cause kidney issues in rats and liver changes in dogs. In humans, it may cause severe liver problems, especially when used with certain other cancer treatments. ^{1 2 6 7 8}

What makes the drug sotorasib unique for treating solid tumors?

Sotorasib is unique because it specifically targets the KRAS G12C mutation, which is a common mutation in certain cancers like non-small cell lung cancer. It is the first drug of its kind to be approved for this mutation, offering a new option for patients who have already tried other treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Adults over 18 with advanced solid tumors that have a specific KRAS p.G12C mutation can join this trial. They must be able to take oral medication and should not have active brain metastases from non-brain tumors or a recent heart attack within the past six months.

Inclusion Criteria

My cancer is advanced or has spread, and tests show a KRAS p.G12C mutation.

Exclusion Criteria

I have brain metastases not originating from a brain tumor.

I cannot take pills due to my GI condition.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants receive sotorasib monotherapy to determine the maximum tolerated dose and recommended phase 2 dose

21 days

Multiple visits for dose escalation and monitoring

Dose Expansion

Participants receive sotorasib monotherapy or combination therapy to evaluate safety and efficacy

24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Sotorasib (AMG 510)

Trial Overview The trial is testing Sotorasib's safety and how well it works in treating solid tumors with the KRAS mutation. It will also determine the highest dose patients can tolerate without severe side effects, as well as an optimal phase 2 dose.

Participant Groups

Group I: Phase 2 monotherapy dose comparison Experimental Treatment 1 Intervention

Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy

Group II: Phase 1 monotherapy treatment naive advanced NSCLC Experimental Treatment 2 Interventions

Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days.

Group III: Phase 1 combination arm with sotorasib and anti PD-1/L1 Experimental Treatment 2 Interventions

Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)

Group IV: Phase 1 Dose Exploration Part 1 monotherapy Experimental Treatment 1 Intervention

Cohorts with food effect and alternative dosing regimens Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort

Group V: Phase 1 Dose Expansion Part 2 monotherapy Experimental Treatment 1 Intervention

Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently

Group VI: Phase 1 Does escalation and Expansion monotherapy BID Experimental Treatment 1 Intervention

BID 2L+solid tumors (fed state)

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

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 (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]

Sotorasib is an irreversible small molecule inhibitor specifically targeting the KRAS G12C mutation, which is found in 13% of lung adenocarcinomas, and has shown significant tumor regression in preclinical studies and clinical trials.

In a reported case, a patient with metastatic KRAS G12C-mutated NSCLC responded remarkably well to sotorasib as a first-line therapy, suggesting its potential as an effective initial treatment option for this type of cancer, particularly in patients with additional health challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib as First-Line Treatment for Advanced KRAS G12C-Mutated Non-Small Cell Lung Carcinoma: A Case Report. Iska, S., Alley, EW.[2023]

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 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 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]

In a study of 102 patients with advanced KRASG12C-mutant NSCLC, those who received sequential anti-PD-(L)1 therapy before sotorasib treatment experienced significantly higher rates of severe adverse events (AEs), with 50% of the sequence group reporting severe AEs compared to only 13% in the control group.

Severe hepatotoxicity was particularly concerning, occurring in 67% of patients in the sequence group, which was three times more frequent than in the control group, highlighting the need to avoid starting sotorasib within 30 days of the last anti-PD-(L)1 infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer. Chour, A., Denis, J., Mascaux, C., et al.[2023]

References

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

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

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

Sotorasib: First Approval. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Sotorasib as First-Line Treatment for Advanced KRAS G12C-Mutated Non-Small Cell Lung Carcinoma: A Case Report. [2023]

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

Sotorasib Edges Closer to Approval. [2021]

5. 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]

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

Nonclinical Safety Profile of Sotorasib, a KRASG12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C-Mutated Cancer. [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

Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer. [2023]