HBI-2438 for Cancer with KRAS G12C Mutation

Recruiting at 13 trial locations

Overseen By Gloria Lee, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HUYABIO International, LLC.

Must not be taking: Steroids, Immunosuppressants, KRAS inhibitors

Disqualifiers: Concurrent malignancy, CNS metastases, Cardiovascular disease, Autoimmune diseases, others

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

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests HBI-2438, an oral drug for patients with advanced solid tumors having the KRAS G12C mutation. The drug aims to stop cancer growth by blocking the faulty gene. Related drugs, Adagrasib and Sotorasib, have shown effectiveness in treating similar conditions.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the trial.

What data supports the effectiveness of the drug HBI-2438 for cancer with KRAS G12C mutation?

KRAS G12C inhibitors have shown promising results in treating non-small cell lung cancer (NSCLC) with this mutation, improving survival and quality of life. The drug sotorasib, a KRAS G12C inhibitor, has been approved for use in NSCLC, indicating potential effectiveness of similar drugs like HBI-2438. ^{1 2 3 4 5}

What makes the drug HBI-2438 unique for treating cancer with KRAS G12C mutation?

HBI-2438 is unique because it targets the KRAS G12C mutation, which is a common driver in certain cancers like lung and colorectal cancer. This mutation-specific approach is part of a new wave of treatments that have been difficult to develop until recently, offering a promising option for patients with this specific genetic mutation. ^{1 2 6 7 8}

Research Team

Alberto Bessudo, MD

Principal Investigator

California Cancer Associates for Research and Excellence, Inc. (cCare)

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific genetic change called KRAS G12C mutation. They should be able to swallow pills, have at least one measurable tumor, and good organ function. They must not benefit from standard treatments and should not have serious heart issues or unresolved severe side effects from past cancer therapy.

Inclusion Criteria

I can swallow pills and don't have major stomach or intestine issues.

At least 1 measurable target lesion that meets the definition of RECIST v1.1

I am fully active or can carry out light work.

Exclusion Criteria

I have brain metastases but haven't needed steroids for them in the last 4 weeks.

I have not been treated with KRAS G12C inhibitors before.

I haven't taken high-dose steroids or immunosuppressants in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive HBI-2438 in ascending doses to determine the maximum tolerated dose

21 days per cycle

Multiple visits for dose escalation monitoring

Expansion

Additional participants with brain metastases receive HBI-2438 at the recommended dose

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Treatment Details

Interventions

• HBI-2438

Trial Overview The study tests different doses of HBI-2438 in patients to find the highest dose they can take without too many side effects (maximum tolerated dose) and to see how the body processes the drug (pharmacokinetic profile).

Participant Groups

Group I: Dose Escalation and Expansion Experimental Treatment 1 Intervention

HBI-2438 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6-8 patients will then be enrolled in the expansion cohort at the recommended dose.

Who Is Running the Clinical Trial?

HUYABIO International, LLC.

Lead Sponsor

Trials

12

Recruited

960+

Findings from Research

In a study of 604 patients with surgically resected lung adenocarcinoma, those with KRASG12C mutations experienced worse disease-free survival (DFS) compared to patients with other KRAS mutations, indicating a more aggressive disease course.

KRASG12C tumors exhibited higher rates of lymphovascular invasion and a greater tumor mutation burden, suggesting that these tumors have distinct and more aggressive genomic features, highlighting the need for targeted therapies like KRASG12C inhibitors to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KRAS G12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma. Jones, GD., Caso, R., Tan, KS., et al.[2022]

In a study of non-small cell lung cancer (NSCLC) patients, up to 8% had co-occurring KRAS mutations alongside the common KRAS G12C mutation, which can affect treatment outcomes.

The presence of additional KRAS mutations, particularly KRAS c.35G>T, led to resistance against the G12C-specific inhibitor AZ'8037, indicating that comprehensive genotyping of KRAS mutations is crucial for effective treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant KRAS mutations attenuate sensitivity of non-small cell lung cancer cells to KRAS G12C inhibition. Vaclova, T., Chakraborty, A., Sherwood, J., et al.[2022]

KRAS G12C mutations are important in several cancers, particularly non-small cell lung cancer (NSCLC), where targeted therapies have shown more success compared to colorectal (CRC) and pancreatic ductal adenocarcinoma (PDAC).

The review discusses the biochemical mechanisms of KRAS targeting, treatment resistance, and ongoing clinical trials for KRAS G12C inhibitors in CRC, indicating a need for further research to improve therapeutic outcomes in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer. Qunaj, L., May, MS., Neugut, AI., et al.[2023]

In a study of 1,194 patients with KRAS-mutant non-small cell lung cancer (NSCLC), 46% had KRAS G12C mutations, which were associated with a higher tumor mutation burden and PD-L1 expression compared to non-G12C mutations.

Despite these differences, the overall survival rates and responses to therapies, including immune checkpoint inhibitors, were similar between patients with KRAS G12C and non-G12C mutations, suggesting that treatment strategies should be tailored to the specific characteristics of KRAS G12C mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C-Mutant Non-Small Cell Lung Cancer. Arbour, KC., Rizvi, H., Plodkowski, AJ., et al.[2022]

The KRASp.G12C mutation, found in 12% of advanced non-small cell lung cancer (NSCLC) cases, is a promising biomarker for selecting patients who may benefit from targeted therapies like sotorasib, which has shown significant efficacy in improving progression-free survival and quality of life compared to traditional treatments.

Despite the potential of KRAS inhibitors, the presence of co-mutations and resistance mechanisms in KRAS mutant NSCLC complicates treatment, highlighting the need for combination therapies and the identification of predictive biomarkers to personalize treatment strategies for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting KRASp.G12C Mutation in Advanced Non-Small Cell Lung Cancer: a New Era Has Begun. Bungaro, M., Novello, S., Passiglia, F.[2023]

KRAS mutations are found in about 30% of all cancers and nearly 50% of metastatic colorectal cancer cases, playing a crucial role in cancer progression by activating pathways that promote cell growth and migration.

The KRAS p.G12C mutation is linked to a poorer prognosis in metastatic colorectal cancer and is emerging as a promising target for new therapies, highlighting the potential for developing specific inhibitors to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KRAS p.G12C Mutation in Metastatic Colorectal Cancer: Prognostic Implications and Advancements in Targeted Therapies. Ottaiano, A., Sabbatino, F., Perri, F., et al.[2023]

KRAS is a commonly mutated oncogene in aggressive solid tumors like colorectal, lung, and pancreatic cancer, making it a critical target for cancer treatment.

Recent advancements have led to the approval of specific inhibitors for the KRAS G12C mutation, such as adagrasib and sotorasib, for treating lung cancer, marking a significant step forward in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Mutated KRAS Genes to Treat Solid Tumours. Krishnan, T., Roberts-Thomson, R., Broadbridge, V., et al.[2022]

The discovery of the KRAS G12C inhibitor represents a significant advancement in treating cancers with KRAS mutations, which were previously considered 'undruggable' due to the instability of RAS proteins.

Combining KRAS G12C inhibitors with immune checkpoint inhibitors (ICIs) may enhance treatment efficacy and help overcome resistance in patients with KRAS-mutant cancers, highlighting a promising new strategy in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting KRAS: Crossroads of Signaling and Immune Inhibition. Kato, S., Fujiwara, Y., Hong, DS.[2022]

References

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

KRAS G12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma. [2022]

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

Concomitant KRAS mutations attenuate sensitivity of non-small cell lung cancer cells to KRAS G12C inhibition. [2022]

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

Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer. [2023]

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

Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C-Mutant Non-Small Cell Lung Cancer. [2022]

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

Targeting KRASp.G12C Mutation in Advanced Non-Small Cell Lung Cancer: a New Era Has Begun. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

KRAS p.G12C Mutation in Metastatic Colorectal Cancer: Prognostic Implications and Advancements in Targeted Therapies. [2023]

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

Targeting Mutated KRAS Genes to Treat Solid Tumours. [2022]

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

Targeting KRAS: Crossroads of Signaling and Immune Inhibition. [2022]