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About
This phase II trial tests how well photoimmunotherapy (PIT) with ASP-1929 in combination with cemiplimab works in treating patients with stage IIIB-IV non-small cell lung cancer (NSCLC) that has not responded to previous treatment (refractory), that is not suitable for surgery (inoperable), or that has spread from where it first started to other places in the body (metastatic). PIT is a treatment that combines drugs that become active when exposed to light, such as ASP-1929, with immunotherapy to target and kill tumor cells. ASP-1929 combines cetuximab with a light-sensitive component, sarotalocan. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called epidermal growth factor receptor (EGFR), which is found on some types of tumor cells. This may help keep tumor cells from growing. Sarotalocan is a fluorescent dye, infrared-activated fluorescent dye 700, that is light sensitive, and when activated by a special type of laser light, helps destroy or change tumor cells. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving PIT with ASP-1929 in combination with cemiplimab may kill more tumor cells in patients with refractory, inoperable, or metastatic stage IIIB-IV NSCLC.
Full description
PRIMARY OBJECTIVE:
I. To assess objective response rate of tumors and lymph nodes following photoimmunotherapy and anti-PD1.
SECONDARY OBJECTIVES:
I. Overall survival following photoimmunotherapy and anti-PD1. II. To assess median progression free survival following photoimmunotherapy and anti-PD1.
III. To assess the relationship between light irradiance and fluence dose volume histograms and objective tumors response following photoimmunotherapy and anti-PD1.
IV. To evaluate the safety of cetuximab sarotalocan sodium (ASP-1929) photoimmunotherapy in combination with immune checkpoint inhibitors in patients with refractory inoperable and metastatic non-small cell lung cancer.
EXPLORATORY OBJECTIVES:
I. To assess the relationship between changes of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) levels and objective response of tumors.
II. To assess the relationship between levels of EGFR expression and the objective response of tumors.
OUTLINE:
Patients receive cemiplimab intravenously (IV) over 30 minutes on days 1, 22, and 43 of each cycle and ASP-1929 IV over 2 hours on day 8 of each cycle. Patients undergo external beam (EB)-PIT via standard of care video-assisted thoracic surgery (VATS) once on day 9 of cycle 1 or interstitial (I)-PIT via endobronchial ultrasound (EBUS) or robotic bronchoscopy up to 3 times on day 9 of cycles 1, 2, and/or 3. Cycles repeat every 9 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, computed tomography (CT) and/or positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
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Inclusion criteria
Exclusion criteria
Has received an investigational agent within 30 days prior to initial treatment or less than 4 half-lives of a previous drug
Had a major surgery, (e.g., requiring general anesthesia) within 4 weeks before the first dose of study treatment or, will not have fully recovered from surgery prior to the first dose
Patients who received chemotherapy or chemoimmunotherapy within 21 days or those who have not recovered from reversible adverse events prior to the scheduled surgery and interstitial or intraoperative PIT
The participants received high dose or curative radiotherapy to the target tumor/s within 30 days prior to the planned I-PIT or EB-PIT
Toxicity related to prior anticancer therapy that has not returned to grade ≤ 1 or baseline levels (except for alopecia, vitiligo, grade ≤ 2 peripheral neuropathy, and endocrinopathies that are stable on hormone replacement, which may be grade 2)
History of immune-related adverse events (irAEs) from prior anticancer therapy leading to permanent treatment discontinuation
History of solid organ or hematologic stem cell transplantation
Prolonged corrected QT interval by Fredericia (QTcF) > 470 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (e.g., placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate or abnormalities in conduction or morphology of electrocardiogram [ECG] [e.g., complete left bundle branch block, third- or second-degree heart block, PR interval > 250 msec]). Note: Participants with cardiac pacemakers who are clinically stable are eligible
Clinically significant cardiovascular disease, including any of the following within 6 months prior to signature of informed consent:
Active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures
Patients with untreated or symptomatically unstable treated brain metastases or history of leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated and stable brain metastases (at least 28 days from last radiotherapy treatment) are eligible as long as steroids are not required for symptom management
Known history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Exceptions include past or resolved hepatitis B (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B virus surface antigen [HBsAg]) and patients positive for hepatitis C (hepatitis C virus [HCV]) antibody if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). HIV testing is not required in absence of clinical suspicion of HIV
History of, or active autoimmune disorder, requiring systemic steroids or immunosuppressive agents. Exceptions allowed: Patients with autoimmune dermatologic conditions not requiring systemic steroids or immunosuppressive agents (e.g. vitiligo, eczema, etc.), endocrine-related autoimmune conditions receiving appropriate hormonal supplementation
History of significant (≥ grade 3) cetuximab infusion reactions
Evidence of interstitial lung disease or current active, noninfectious pneumonitis
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive ASP-1929
Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive the experimental PIT or immunotherapy
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
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27 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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