Ladarixin With Sotorasib in Advanced NSCLC

Recruiting now · Phase 1

Conditions studied: Advanced Non-small Cell Lung Cancer With KRAS G12C Mutation

In brief

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).

Key facts

Study ID

NCT05815173

Run by

NYU Langone Health

People needed

40

Starts

2023-08-01

Expected to finish

2027-08-01

Last updated by the study team

2025-12-30

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

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
• Serum bilirubin ≤1.5 × upper limit of normal (ULN), or ≤ 3.0 × ULN for subjects with Gilbert's Syndrome
• AST and ALT ≤ 2x upper limit of normal (ULN)
• International normalization ratio (INR) <1.5 if the patient is not on anticoagulants, or INR <3 after dose titration has been completed if the patient is on anticoagulants.
• Renal clearance as estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) Study equation ≥50 mL/min/1.73m2.
• Persons of childbearing potential (POCBP, defined as a sexually mature person assigned female at birth) must have a negative serum pregnancy test prior to study entry. Women of non-childbearing potential will have had at least 12 continuous months of natural (spontaneous) amenorrhea, and an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms), or have had surgical bilateral oophorectomy, hysterectomy, or bilateral tubal ligation >6 weeks prior to Screening.
• Persons assigned male at birth or persons assigned female at birth participants: Persons assigned male at birth participants with partners of childbearing potential and participants of childbearing potential are required to use 2 forms of acceptable contraception, including 1 barrier method, during their participation in the study and for 3 months following last dose. Persons assigned male at birth participants must also refrain from donating sperm during their participation in the study and for 12 months after the last dose of study medication.
• Participants must be able to swallow and retain orally administered medication.

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.
• Nonmalignant decompensated liver disease.
• Significant gastrointestinal abnormalities or a chronic condition, including inability to swallow the formulated product, delayed gastric emptying, chronic active Crohn's disease that requires steroid therapy at any dose, refractory nausea and vomiting, and/or prior surgical procedures affecting absorption or requirement for intravenous alimentation.
• History (≤6 months before the start of treatment with the study drugs) of any of the following: acute myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident.
• Participants who have impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Significant ventricular or supraventricular arrhythmias (patients with sinus arrhythmia or chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
• Left ventricular ejection fraction (LVEF) <50% assessed by echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 6 months before the start of treatment with the study drugs and at screening.
• Resting bradycardia (<50 beats per minute) determined as the mean of 3 heart rate values from the screening triplicate 12-lead electrocardiograms (ECGs) obtained.
• Other clinically significant heart disease such as congestive heart failure New York Heart Association Class II-IV.
• Participants with QT interval >470 msec at screening using Fridericia's formula (QTcF), determined as the mean of 3 QTcF values from the screening triplicate ECG.
• Known history (≤6 months before the start of treatment with the study drugs) of significant inflammatory eye disease, central serous retinopathy, uveitis, or evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome).

Where it is running

• NYU Langone Health — Mineola, New York, United States (enrolling)
• NYU Langone Health — New Hyde Park, New York, United States (enrolling)
• NYU Langone Health — New York, New York, United States (enrolling)
• NYU Langone Health — New York, New York, United States (enrolling)
• NYU Langone Health — New York, New York, United States (enrolling)
• NYU Langone Health — Garden City, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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