Sotorasib for Brain Tumors

Recruiting at 6 trial locations

Overseen By Nelson Moss, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Allergy to study treatment, Multiple malignancies, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period (time without taking certain medications) from prior therapies to allow recovery from any prior treatment-related toxicities before enrollment. This suggests you may need to stop some current medications, but the specific details should be discussed with the trial investigator.

What data supports the effectiveness of the drug Sotorasib for brain tumors?

Sotorasib targets the Ras signaling pathway, which is often overactive in brain tumors, similar to other drugs like tipifarnib that have been tested for brain tumors. This suggests that Sotorasib might also be effective in treating brain tumors by targeting this pathway. ^{1 2 3 4 5}

Is sotorasib safe for humans?

Sotorasib has been approved for use in certain lung cancers, indicating it has been evaluated for safety in humans. While specific safety data for brain tumors is not detailed, its approval suggests a general safety profile in humans. ^{6 7 8 9 10}

How is the drug Sotorasib unique for treating brain tumors?

Sotorasib is unique because it targets a specific mutation (KRAS G12C) and has shown promising results in treating brain metastases, even in patients who have not received prior treatment for these metastases. This is notable because many treatments do not effectively address brain metastases, making Sotorasib a potentially valuable option for patients with this specific genetic mutation. ^{6 7 8 9 11}

What is the purpose of this trial?

The researchers are doing this study to find out how effective sotorasib is at getting into KRAS G12C+ brain tumors. The researchers will also find out whether sotorasib is a safe and effective treatment for people undergoing surgical resection of KRAS G12C+ metastatic brain tumors, and do tests that show how the body absorbs, distributes, and gets rid of sotorasib.

Research Team

Nelson Moss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals with brain tumors that have a specific mutation called KRAS G12C+. Participants should be scheduled for surgical removal of their metastatic brain tumors. The study will include tests to understand how the body handles sotorasib.

Inclusion Criteria

I am 18 or older and scheduled for brain tumor surgery.

Life expectancy >12 weeks

I can care for myself but may need occasional help.

Exclusion Criteria

I am not allergic to the study drug or its components.

I haven't had any new cancers in the last 3 years, except for minor skin cancers or early-stage cancers that were fully treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotorasib to evaluate its penetration into KRAS G12C+ brain tumors and its safety and effectiveness during surgical resection

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotorasib

Trial Overview The study is testing the effectiveness and safety of a drug named Sotorasib on patients with KRAS G12C+ brain tumors. It aims to see if the drug can reach the tumor effectively and assess its impact before and after surgery.

Participant Groups

Group I: DCOI naïve Experimental Treatment 1 Intervention

Will receive the standard dose of sotorasib.

Group II: Progressed on the DCOI Active Control 1 Intervention

Will continue to receive the sotorasib dose they were previously receiving, according to their doctor's instruction.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Amgen

Industry 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 III clinical trial involving 325 patients with recurrent glioblastoma, cediranib did not significantly improve progression-free survival compared to lomustine alone, whether used as a monotherapy or in combination.

Despite not meeting the primary endpoint, cediranib demonstrated some clinical benefits in secondary outcomes, such as delaying neurological deterioration and reducing the need for corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. Batchelor, TT., Mulholland, P., Neyns, B., et al.[2022]

Targeted therapies, such as receptor tyrosine kinase inhibitors and farnesyl transferase inhibitors, are being investigated to address the abnormal growth factor signaling pathways that contribute to brain tumor development, which are often resistant to traditional treatments.

Clinical trials are currently testing several of these targeted agents, including imatinib mesylate and gefitinib, in patients with high-grade gliomas, aiming to improve survival and quality of life for those affected by these aggressive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. Newton, HB.[2007]

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

The maximum tolerated dose (MTD) of vandetanib when combined with fractionated stereotactic radiosurgery (SRS) for patients with recurrent malignant gliomas was determined to be 100 mg daily, as this dose resulted in less than 33% of patients experiencing dose-limiting toxicities.

In a study involving 10 patients, 6 showed a radiographic response to treatment, indicating potential efficacy of the combination therapy, although further evaluation is needed to confirm safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. Fields, EC., Damek, D., Gaspar, LE., et al.[2022]

The maximum tolerated dose of sorafenib (Sb) in combination with radiation therapy and temozolomide was established at 200 mg taken twice daily, with dose-limiting toxicities including thrombocytopenia and diarrhea.

Despite the combination treatment showing a median progression-free survival of 7.9 months and overall survival of 17.8 months, the significant side effects and moderate outcomes suggest that further clinical development of Sb for malignant gliomas may not be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. Hottinger, AF., Ben Aissa, A., Espeli, V., et al.[2021]

In a study of 30 patients with KRAS-mutated non-small cell lung cancer and brain metastases, sotorasib showed varying effectiveness based on the status of brain metastases, with a median intracranial progression-free survival of 15 months for patients with stable brain metastases, compared to only 3 months for those with active metastases without recent local therapy.

Although sotorasib demonstrated some intracranial activity, 57% of patients experienced progression, highlighting the need for a comprehensive treatment approach for brain metastases and suggesting that further research with larger cohorts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief report on the efficacy of sotorasib in KRAS-Mutated NSCLC patients with brain metastases. Lebouille-Veldman, AB., Taros, TN., Nawabi, NLA., et al.[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]

Sotorasib has demonstrated significant efficacy in treating KRAS G12C-mutated non-small-cell lung carcinoma (NSCLC), showing complete responses and stabilization of brain metastases in patients with previously treated, stable conditions.

A specific case highlighted a patient with active untreated brain metastases who experienced nearly complete intracranial response just 6 weeks after starting sotorasib, suggesting its potential effectiveness in previously untreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Shows Intracranial Activity in Patients with KRAS G12C-Mutated Adenocarcinoma of the Lung and Untreated Active Brain Metastases. Koster, KL., Appenzeller, C., Lauber, 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]

References

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

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. [2007]

3. England pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. [2023]

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

Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Brief report on the efficacy of sotorasib in KRAS-Mutated NSCLC patients with brain metastases. [2023]

7. 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]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Sotorasib Shows Intracranial Activity in Patients with KRAS G12C-Mutated Adenocarcinoma of the Lung and Untreated Active Brain Metastases. [2022]

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

Sotorasib: First Approval. [2022]

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

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