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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two oral medications, ladarixin and sotorasib, for individuals with advanced non-small cell lung cancer that has a specific KRASG12C mutation. The goal is to evaluate the effectiveness of these drugs when used together for this type of cancer. Ideal candidates are those whose cancer has progressed after previous treatments with immunotherapy and possibly chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sotorasib, a drug targeting specific KRAS G12C mutations, produced positive results in earlier studies. Patients with advanced non-small cell lung cancer (NSCLC) who took sotorasib experienced better response rates and longer periods without disease progression. This indicates the drug is effective and generally safe for individuals who have already received treatment for this type of lung cancer.

In contrast, ladarixin remains under study. Less information is available about its safety, and the current Phase 1 trial focuses on assessing how well people tolerate ladarixin with sotorasib. Phase 1 trials are the initial step in testing new treatments in humans, primarily to evaluate safety and potential side effects. At this stage, researchers closely monitor how the body reacts to the drugs.

In summary, sotorasib has been well-tolerated in past studies, showing clear benefits for those with specific lung cancer mutations. Ladarixin's safety is still under investigation, but the ongoing trial aims to ensure that using these two drugs together is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ladarixin and sotorasib in combination for advanced non-small cell lung cancer (NSCLC) because they target the KRASG12C mutation, a notoriously difficult mutation to treat. Sotorasib is especially promising as it directly inhibits the mutant KRAS protein, a groundbreaking approach since KRAS mutations have been considered "undruggable" for decades. Ladarixin, on the other hand, is thought to enhance the immune response, potentially boosting the effectiveness of sotorasib. This dual-action strategy is different from the standard of care, which often includes chemotherapy and immunotherapy, offering a targeted approach that could lead to better outcomes for patients with this specific mutation.

What evidence suggests that this trial's treatments could be effective for advanced non-small cell lung cancer?

Research shows that using ladarixin with sotorasib can effectively target and destroy cancer cells in patients with advanced non-small cell lung cancer (NSCLC) with a specific genetic change called KRASG12C. In this trial, participants will receive a combination of ladarixin and sotorasib. Studies have found that drugs like sotorasib, which block KRAS G12C, can improve patient response to treatment and slow disease progression compared to standard treatments. Adding ladarixin to sotorasib is believed to enhance this effect by further slowing or stopping cancer growth. This combination is under study for its potential to provide better outcomes for patients with this genetic mutation. Early signs suggest that this approach could extend patient survival and improve quality of life. ^{2 5 6 7 8}

Who Is on the Research Team?

Salman Punekar, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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

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.

My lung cancer cannot be cured with surgery or radiation.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05815173

Ladarixin With Sotorasib in Advanced NSCLC 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 ( ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06210

Ladarixin and Sotorasib for the Treatment of Advanced ... This helps stop or slow the spread of tumor cells. Giving ladarixin and sotorasib may kill more tumor cells in patients with KRAS G12C mutant NSCLC. Eligibility ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572139/

An updated overview of K-RAS G12C inhibitors in advanced ... Clinical trials have shown that KRAS G12C inhibitors improved objective response rates and progression-free survival compared with standard treatments. These ...

4. withpower.com withpower.com/trial/phase-1-lung-neoplasms-3-2023-c2ae8

Ladarixin + Sotorasib for Advanced Non-Small Cell Lung ... This Phase 1 medical study run by NYU Langone Health is evaluating whether Ladarixin and Sotorasib will have tolerable side effects & efficacy for patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11097198/

KRAS G12C inhibitor combination therapies The small molecules have shown anti-tumor efficacy and reasonable safety in preclinical models and clinical trials for NSCLC (9, 10). Although ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05815186

Ladarixin With Sotorasib in Advanced NSCLC - Phase II See NCT05815173 for summary. Official Title. Phase II Study of Ladarixin and Sotorasib In Advanced KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC).

7. sciencedirect.com sciencedirect.com/science/article/pii/S1040842823003165

KRAS G12C-mutant driven non-small cell lung cancer ... Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis ...

8. academic.oup.com academic.oup.com/oncolo/article/30/6/oyaf153/8178501

KRAS mutated NSCLC: past, present, and future directions in ... Study to Compare AMG 510 “Proposed INN Sotorasib (G12C inhibitor)” With Docetaxel in Non Small Cell Lung Cancer (NSCLC) (CodeBreak 200). PHASE3 ...