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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sotorasib, a targeted therapy for brain tumors with the KRAS G12C+ mutation. The main goal is to determine if sotorasib can effectively reach these tumors and assess its safety for patients requiring surgery to remove their brain tumors. The trial includes two groups: one will receive a standard dose of sotorasib, while the other will continue their current dose if they have already been receiving it. Ideal participants are adults with at least one brain tumor needing surgery and possibly additional tumors in the brain or surrounding areas. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that sotorasib is likely to be safe for humans?

Research has shown that sotorasib, a treatment for certain cancers, is generally well-tolerated by patients. It is already approved for use in other cancers, such as non-small cell lung cancer, where it has benefited 28% to 37% of patients, indicating many experience positive effects.

Safety data from various studies suggest that sotorasib is safe for patients, even those with cancer that has spread to the brain. Patients report similar safety outcomes regardless of brain tumor presence, demonstrating consistent safety across different groups.

While side effects can occur, the drug's approval for other conditions indicates a strong safety record. However, as this trial is in its early stages, more data is needed to confirm these findings specifically for brain tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often involve surgery, radiation, and chemotherapy, sotorasib offers a targeted approach by specifically inhibiting the KRAS G12C mutation. This mutation is a driver in many cancers, and sotorasib is one of the first treatments to directly target it, potentially providing a more effective and less invasive option. Researchers are excited about sotorasib because it represents a new class of targeted therapies that could lead to better outcomes for patients whose tumors harbor this specific genetic mutation.

What evidence suggests that sotorasib might be an effective treatment for brain tumors?

Studies have shown that sotorasib works well for certain cancers with KRAS G12C mutations. For individuals with advanced non-small cell lung cancer (NSCLC), sotorasib shrank tumors in 28% to 37% of patients. It also extended the time patients lived without their cancer worsening, averaging about 5.6 to 6.8 months. In cases where cancer had spread to the brain, sotorasib reduced tumor size in 33.3% of patients. As the first drug to specifically target the KRAS G12C mutation, it has shown promising results in these challenging cancers. Participants in this trial will receive sotorasib, either as a standard dose for those who are DCOI naïve or as a continued dose for those who have progressed on the DCOI, following their doctor's instructions. ^{6 7 8 9 10}

Who Is on the Research Team?

Nelson Moss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000826

Real-world effectiveness and tolerability of sotorasib in ... Brain metastases were present in 38.0 % of patients, with 55.2 % showing progression at sotorasib initiation. PD-L1 expression levels were ≤ 1 % ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10309542/

Incidence of Brain Metastases and Preliminary Evidence of ... Sotorasib is the first approved drug for metastatic KRAS G12C-mutant NSCLC, with a response rate of 28%-37% and median progression-free survival of 5.6-6.8 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.17_suppl.LBA9016

Intracranial efficacy of sotorasib versus docetaxel in ... Sotorasib was the first oral KRAS G12C inhibitor to show improved progression-free survival (PFS) and overall response rate (ORR), with a better toxicity ...

4. actr.amegroups.org actr.amegroups.org/article/view/9710/html

Intracranial efficacy of adagrasib in patients with KRAS G12C ... Among those with measurable CNS metastases for RANO-BM evaluation, response rate of 33.3% was noted for sotorasib (n=18) versus 15.4% for ...

5. jto.org jto.org/article/S1556-0864(21)02970-1/fulltext

P52.03 Efficacy of Sotorasib in KRAS p.G12C-Mutated ... In the registrational phase 2 part, sotorasib showed an objective response rate (ORR) of 37.1% and a median progression-free survival (PFS) of 6.8 months. Here, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225005756

Intracranial activity of sotorasib vs docetaxel in pretreated ... To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9719091/

Remarkable Intracranial Response to Sotorasib in a Patient ... We report a case of KRAS G12C -mutated NSCLC with active, untreated brain metastases having profound clinical and radiographic response to sotorasib.

8. jto.org jto.org/article/S1556-0864(22)01629-X/fulltext

PP01.17 Sotorasib in Advanced KRAS p.G12C–Mutated ... In this focused analysis on patients with brain metastases in the sotorasib EAP, safety and efficacy data were similar across patients with and without brain ...

9. ascopubs.org ascopubs.org/doi/10.1200/PO.22.00621

Mutant Non–Small-Cell Lung Cancer Sotorasib is the first approved drug for metastatic KRAS G12C-mutant NSCLC, with a response rate of 28%-37% and median progression-free survival of 5.6-6.8 ...

10. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02967-2/fulltext

989P Sotorasib in advanced KRAS p.G12C-mutated non- ... 989P Sotorasib in advanced KRAS p.G12C-mutated non-small cell lung cancer (NSCLC): Safety and efficacy data from the global expanded access program (EAP).