Ladarixin With Sotorasib in Advanced NSCLC

NCT05815173 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-00959
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Advanced Non-small Cell Lung Cancer With KRAS G12C Mutation

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicities (DLTs) during 1st Treatment Cycle among Phase I Participants

  DLTs are defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

  Up to Day 21 (End Treatment Cycle 1, each cycle is 21 days)

• Progression Free Survival (PFS)

  PFS is the amount of time (months) from initial treatment to disease progression or death from any cause.

  Up to End of Survival Follow-Up (Up to Month 36)

Secondary Outcomes (10)

• Percent of Participants who Experience Grade 5 Treatment-Related Adverse Events per CTCAE 5.0

  Up to End of Survival Follow-Up (Up to Month 36)

• Percent of Participants who Experience Grade 4 Treatment-Related Adverse Events per CTCAE 5.0

  Up to End of Survival Follow-Up (Up to Month 36)

• Percent of Participants who Experience Grade 3 Treatment-Related Adverse Events per CTCAE 5.0

  Up to End of Survival Follow-Up (Up to Month 36)

• Percent of Participants who Experience Grade 2 Treatment-Related Adverse Events per CTCAE 5.0

  Up to End of Survival Follow-Up (Up to Month 36)

• Percent of Participants who Experience Grade 1 Treatment-Related Adverse Events per CTCAE 5.0

  Up to End of Survival Follow-Up (Up to Month 36)

Study Arms (1)

Advanced NSCLC Patients

EXPERIMENTAL

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

Drug: Sotorasib; Drug: Ladarixin

Interventions

Sotorasib DRUG

Sotorasib administered at the approved dose of 960mg PO once daily over 21-day treatment cycles.

Advanced NSCLC Patients

Ladarixin DRUG

Ladarixin dose will be escalated as follows in Phase I: 3 patients will receive a starting dose of 200mg. If 2 or more patients experience a DLT at the lowest dose, the study will stop. If 0 out of 3 patients experience a DLT within 28 days, the next 3 patients will receive 300mg. If 1 out of 3 patients experiences a DLT, 3 more patients will be added to the 200 mg dose. If no more patients experience a DLT at 200mg, the next 3 patients will receive 300mg. If 2 of 6 patients receiving 200mg experience a DLT, the study will stop. If 2 or more patients experience DLTs, the maximum tolerated dose (MTD) will be the previous dose level. The same process will be repeated at each dose level. There will be 6 patients enrolled at MTD level for a maximum of 12 patients in the phase I cohort. Ladarixin will be administered as a twice-daily dose over a 21 day treatment cycle. In Phase II, ladarixin will be administered twice-daily at the recommended phase II dose over 21-day cycles.

Advanced NSCLC Patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participant must be ≥18 years of age at the time of signature of the informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous).
• Patients with metastatic or locally advanced NSCLC who are not candidates for curative surgery or curative radiation.
• Do not have an epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) translocation, rearranged during transfection (RET), ROS1 or other actionable molecular alterations that can be treated with FDA approved targeted agents.
• Patients must have documentation of presence of KRASG12C mutation in tumor tissue.
• Patients must have demonstrated progression of disease following treatment with anti-PD (L)-1 with or without platinum-based chemotherapy.
• Participants must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Tumor lesions that have been irradiated ≥4 weeks before the start of treatment, and have subsequently had documented progression, may be chosen as target lesions in the absence of measurable lesions that have not been irradiated.
• Participants whose laboratory data at Screening meet the following criteria:
• Absolute neutrophil count ≥1.5 × 109/L
• Platelets ≥100 × 109/L
• Hemoglobin ≥8 g/dL without transfusion within 7 days
• Albumin ≥3 g/dL
• Lymphocyte count ≥0.5 × 109/L

You may not qualify if:

• History (≤1 years) or presence of hematological malignancies except stable CLL.
• History (≤1 years) of other cancer that is histologically distinct from the cancers under study, except for cervical carcinoma in situ, ductal carcinoma in situ, prostatic intraepithelial neoplasia, superficial non-invasive bladder tumors, or curatively treated stage I non-melanoma skin cancer.
• Known serious allergy to ladarixin, sotorasib, or excipients (e.g., microcrystalline cellulose).
• History (≤6 months before the start of treatment with the study drugs) of severe autoimmune disease (including ≥ Grade 3 or recurrent Grade 2 immune-related AEs of prior immuno-oncology therapy) or autoimmune disorder that requires chronic systemic corticosteroid treatment at immunosuppressive doses (prednisone \>10 mg/day or equivalent).
• Brain or spinal metastases, except if treated by surgery or surgery plus radiotherapy or radiotherapy alone, with no clinical evidence of progression or hemorrhage for ≤7 days before the start of treatment with the study drugs, and has not received any systemic corticosteroids for ≥7 days before the start of treatment with the study drugs.
• History (≤6 months before the start of treatment with the study drugs) of pericarditis (any grade) or pericardial effusion (Grade ≥2).
• History of interstitial lung disease, radiation pneumonitis which required steroid treatment, idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or organizing pneumonia.
• Active infection requiring systemic treatment at the start of treatment in this trial. A washout period of 7 days after the last dose of antibiotics prior to first dose of study drug is required.
• History of seropositive status for human immunodeficiency virus (HIV) at any time before the start of treatment as determined by presence of anti-HIV-1 or anti-HIV-2 antibodies.
• \-- Note: Testing for seropositive status during Screening will be at the discretion of the investigator in participants without previously reported results.
• Has active hepatitis B, or hepatitis C infection.
• Note: Participants with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection) are permitted. Participants with controlled infections must undergo periodic monitoring of hepatitis B virus DNA.
• Note: Participants who are hepatitis C virus antibody positive (HCV Ab+), who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study. Participants with controlled infections must undergo periodic monitoring of HCV RNA per treating physician.
• 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 such as:
• Nonmalignant illnesses that are uncontrolled or whose control may be jeopardized by this study treatment.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (6)

NYU Langone Health

Garden City, New York, 11530, United States

RECRUITING

NYU Langone Health

Mineola, New York, 11501, United States

RECRUITING

NYU Langone Health

New Hyde Park, New York, 11042, United States

RECRUITING

NYU Langone Health

New York, New York, 10010, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

NYU Langone Health

New York, New York, 10017, United States

RECRUITING

MeSH Terms

Interventions

sotorasib; 2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide

Study Officials

• Salman Punekar, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salman Punekar, MD

CONTACT

212 731 6228; Salman.punekar@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: April 18, 2023
• Study Start: August 1, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to salman.punekar@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (6)