Ladarixin + Sotorasib for Advanced Non-Small Cell Lung Cancer

Recruiting at 3 trial locations

Overseen By Salman Punekar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NYU Langone Health

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Hematological malignancies, Severe autoimmune, Brain metastases, Active infection, others

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

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I/II, open-label, study of twice-daily oral ladarixin with sotorasib in participants with advanced KRASG12C mutant non-small cell lung cancer (NSCLC).

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study drugs. You must stop using drugs that are moderate or strong CYP3A4 inhibitors or inducers, and those metabolized by CYP2C9 with a narrow therapeutic index, at least 14 days before starting the trial. Some medications may be allowed at the investigator's discretion with approval.

What makes the drug Ladarixin + Sotorasib unique for treating advanced non-small cell lung cancer?

The drug combination of Ladarixin and Sotorasib is unique because Sotorasib is a first-in-class inhibitor specifically targeting the KRAS G12C mutation, which is a common mutation in non-small cell lung cancer. This drug works by blocking the signals that promote cancer cell growth, offering a new option for patients who have already undergone other treatments. ^{1 2 3 4 5}

Research Team

Salman Punekar, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRASG12C can join this trial if their disease worsened after anti-PD-1 therapy and/or chemotherapy. They must be able to take pills, have no serious heart issues or infections, not be pregnant or breastfeeding, agree to use contraception, and cannot have had certain other treatments recently.

Inclusion Criteria

I am 18 years old or older.

Written informed consent, according to local guidelines, signed and dated by the participant prior to the performance of any study-specific procedures, sampling, or analyses

I am fully active or can carry out light work.

Exclusion Criteria

I have been treated with KRAS inhibitors before.

History (≤6 months before the start of treatment) of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator and sponsor, could affect the patient's participation in the study

My brain or spinal cancer has been stable for at least 7 days, and I haven't taken steroids in the last 7 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Participants receive ladarixin and sotorasib to determine the recommended phase II dose (RP2D)

3 weeks

1 visit (in-person) per cycle

Treatment Phase II

Participants continue receiving ladarixin and sotorasib to evaluate progression free survival (PFS)

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Treatment Details

Interventions

• Ladarixin
• Sotorasib

Trial Overview The study is testing the combination of two oral drugs: ladarixin and sotorasib. It's for patients whose NSCLC carries the KRASG12C mutation. The trial aims to see how well these drugs work together when taken twice daily by people who've already tried some other treatments.

Participant Groups

Group I: Advanced NSCLC Patients Experimental Treatment 2 Interventions

Patients with KRASG12C mutant NSCLC will receive ladarixin and sotorasib in combination.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

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]

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, 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]

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

Sotorasib: First Approval. [2022]

3. 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]

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

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

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

Sotorasib Edges Closer to Approval. [2021]