Ladarixin + Sotorasib for Advanced Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Salman Punekar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Breakthrough Therapy

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.

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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.

Trial 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

Participant Groups

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.

Group I: Advanced NSCLC Patients Experimental Treatment 2 Interventions

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NYU Langone Health New York, NY

NYU Langone Health New Hyde Park, NY

NYU Langone Health Garden City, NY

NYU Langone Health Mineola, NY

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

References

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

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022] Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor. By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA. A clinically relevant objective response rate was observed in patients with KRAS G12C mutation-positive NSCLC during the primary analysis and in an updated analysis of the phase I/II CodeBreaK 100 trial. Furthermore, a clinically relevant response duration was reported in updated analyses of the trial. Sotorasib has a manageable tolerability profile, with permitted dose modifications to manage toxicity. In summary, sotorasib is a promising KRASG12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.

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

Sotorasib: First Approval. [2022] Sotorasib (LUMAKRAS™) is a RAS GTPase family inhibitor being developed by Amgen for the treatment of solid tumours with KRAS mutations, including non-small cell lung cancer (NSCLC) and colorectal cancer. In May 2021, sotorasib was granted accelerated approval by the US FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This article summarizes the milestones in the development of sotorasib leading to this first approval for KRAS G12C-mutated NSCLC.

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] The efficacy of sotorasib for patients with KRAS G12C-mutated lung cancer with poor performance status (PS) and active brain metastases remains unknown. Here, we present a case in which sotorasib was introduced as the third-line therapy for a patient whose PS worsened due to active multiple brain metastases and disseminated intravascular coagulation (DIC) caused by rapid tumor progression; a marked effect was observed. DIC and PS improved two weeks after the start of the administration, and multiple brain metastases disappeared. The effect lasted only approximately four months due to the development of a new liver metastasis, but sotorasib improved PS and the DIC status was reversed, allowing for further treatment. Sotorasib could be considered for introduction in patients with poor PS.

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

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022] Label="BACKGROUND">Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).

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

Sotorasib Edges Closer to Approval. [2021] The KRASG12C inhibitor sotorasib continues to impress in non-small cell lung cancer: In the phase II CodeBreak 100 trial, the agent elicited responses in more than a third of patients and led to a median progression-free survival of almost 7 months. Based on these results, Amgen has filed for the drug's approval with the FDA and the European Medicines Agency.