Photoimmunotherapy With ASP-1929 and Cemiplimab for the Treatment of Refractory, Inoperable, and Metastatic Stage IIIB-IV Non-small Cell Lung Cancer

Phase II Trial: Photoimmunotherapy and Anti-PD1 in Patients With Refractory Inoperable and Metastatic Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Lung Non-Small Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Biological: Cemiplimab; Procedure: Positron Emission Tomography; Other: Electronic Health Record Review; Procedure: Computed Tomography; Procedure: Video-Assisted Thoracic Surgery; Procedure: Endobronchial Ultrasound Bronchoscopy; Biological: Cetuximab Sarotalocan Sodium; Procedure: Photoimmunotherapy; Procedure: Photoimmunotherapy; Procedure: Robotic Bronchoscopy

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
      • Contact: Prantesh Jain; Phone Number: 716-845-8451; Email: Prantesh.Jain@roswellpark.org
      • Principal Investigator: Prantesh Jain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects with histologically or cytologically confirmed stage IIIB-IV NSCLC
• Subjects lacking actionable genetic mutations must have been previously treated with (a) anti-PD-1/PD-L1 therapy; and (b) platinum-based chemotherapy, either as combination or sequentially for metastatic disease and have progressed on or after therapy. Individuals who cannot tolerate or have previously refused platinum-based chemotherapy or who are unable to receive it are eligible to enroll based on progression after anti-PD-1/PD-L1 therapy alone
• NSCLC with known actionable genomic alteration (e.g., EGFR, ALK, ROS1, BRAF) must have received all approved targeted therapies and have progressed (data capture not necessary for ALK, ROS1, BRAF)
• Subjects have at least two lesions of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• At least one site of disease accessible to photoimmunotherapy. Thus, the therapeutic 690-nm laser light can be administered via insertion of optical fiber/s in the target tumor for interstitial photoimmunotherapy (I-PIT), or target tumors can be illuminated with external beam photoimmunotherapy (EB-PIT)
• Absolute neutrophil count: ≥ 1,000/µL
• Platelets: ≥ 100,000/µL
• Total bilirubin: ≤ institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]): ≤ 3 x institutional ULN
• Creatinine clearance (CrCl) ≥ 50 mL/min (Cockcroft-Gault)
• Patient has not received a transfusion within 2 weeks prior to screening
• Female patients of childbearing potential must have a negative pregnancy test at screening and must be willing to use 2 methods of highly effective birth control while on study or be surgically sterile, or abstain from heterosexual sexual activity for the course of the study through 120 days after the last dose of anti-PD1 treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Male participants must agree to use a highly effective method of contraception starting with the first dose of study medication through 120 days after the last dose of anti-PD1 treatment
• Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedures

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:

  • Myocardial infarction, severe or unstable angina, or coronary artery bypass surgery
  • Clinically significant arrhythmias (e.g., ventricular arrhythmias or atrial fibrillation with uncontrolled heart rate)
  • Congestive heart failure (New York Heart Association [NYHA] class III/IV)
  • Cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
  • Myocarditis
• 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

  • Use of immunosuppressant drugs such as steroids, azathioprine, tacrolimus, cyclosporine, etc. is not permitted within 4 weeks before recruitment (exception allowed is use of steroids as hormone replacement therapy or as supportive medication e.g. anti-emesis, contrast allergy, pre-medication, etc. or other short-course therapy less than 2 weeks continuously within 4 weeks of study treatment)
• 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:

  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included
  • Patients with celiac disease controlled by diet alone
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (photoimmunotherapy, ASP-1929, cemiplimab); Patients receive cemiplimab 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 EB-PIT via standard of care VATS once on day 9 of cycle 1 or I-PIT via 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, CT and/or PET/CT or MRI throughout the study.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; REGN 2810; REGN-2810; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Other: Electronic Health Record Review; Ancillary studies; Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Video-Assisted Thoracic Surgery; Undergo VATS; Other Names: VATS; Video-Assisted Thoroscopic Surgery; Procedure: Endobronchial Ultrasound Bronchoscopy; Undergo EBUS; Other Names: EBUS; Endobronchial Ultrasound; Biological: Cetuximab Sarotalocan Sodium; Given IV; Other Names: ASP 1929; ASP-1929; ASP1929; Cet-IR700; Cetuximab-IR700 Conjugate RM-1929; RM-1929; Procedure: Photoimmunotherapy; Undergo EB-PIT; Other Names: Photodynamic Light Therapy; Procedure: Photoimmunotherapy; Undergo I-PIT; Other Names: Photodynamic Light Therapy; Procedure: Robotic Bronchoscopy; Undergo robotic bronchoscopy; Other Names: Robot-Assisted Bronchoscopy; Robotic-Assisted Bronchoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Will be defined as the proportion of patients who have a partial or complete response to therapy and will be assessed according to immune-modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Will be defined as the time the patient is alive without tumor progression after treatment according to RECIST v 1.1. Will be estimated using the Kaplan-Meier estimator.	From the treatment to time of death from any reason, assessed up to 2 years
Median progression free survival (PFS)	Will be defined as the time the patient is alive without tumor progression after treatment according to RECIST v 1.1. Will be estimated using the Kaplan-Meier estimator. Corresponding median PFS will be estimated along with the respective 95% confidence interval.	Up to 2 years
Relationship between the light irradiance and fluence in the photoimmunotherapy treated tumor and the objective response of treated and untreated tumors	Will be determined by computing the dose volume histogram of the irradiance and fluence in the illuminated tumor/s and measuring the objective tumor response according to RECIST v 1.1. Will be analyzed using multivariate and univariate mixed effects logistic and standard logistic regression modeling.	Up to 2 years
Incidence of adverse events	Will be evaluated in accordance with Common Terminology Criteria for Adverse Events v 5.0.	From the first day of the administration of the ASP-1929 up to 30 days after last treatment of ASP-1929 with cemiplimab

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Rakuten Medical, Inc.
• Investigators: Principal Investigator: Prantesh Jain, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Drug Therapy; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy; Chemistry Techniques, Analytical; Spectrum Analysis; Combined Modality Therapy; Phototherapy; Thoracic Surgical Procedures; Thoracoscopy; Video-Assisted Surgery; Specimen Handling; Magnetic Resonance Spectroscopy; cemiplimab; Photochemotherapy; Thoracic Surgery, Video-Assisted
• Other Study ID Numbers: I-3845023 (Other Identifier: Roswell Park Cancer Institute); NCI-2025-02417 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes