Photoimmunotherapy for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disorders, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with advanced non-small cell lung cancer (NSCLC) that hasn't responded to other treatments. The researchers are examining the effectiveness of a technique called photoimmunotherapy (PIT) combined with the drug cemiplimab. PIT uses a special light-activated drug to target cancer cells, while cemiplimab is an immunotherapy that helps the immune system attack cancer. This trial suits individuals with stage IIIB-IV NSCLC that cannot be treated with surgery and have already tried other treatments without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressant drugs like steroids within 4 weeks before joining the study, unless they are for hormone replacement or short-term use. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that ASP-1929 combined with another type of immune therapy was generally well-tolerated, with most participants experiencing no serious side effects. The study reported no treatment-related deaths. Similarly, research on cemiplimab, another immune therapy, has shown it to be safe for treating advanced lung cancer. Together, these treatments appear safe for patients, with no major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about photoimmunotherapy for lung cancer because it combines the power of light with targeted therapy, offering a unique approach to treatment. Unlike traditional chemotherapy or radiation, which can affect healthy cells, ASP-1929 specifically targets cancer cells, making the treatment potentially more precise and reducing side effects. Moreover, the addition of cemiplimab, an immunotherapy drug, helps the body’s immune system attack cancer cells more effectively. This combination not only targets the tumor directly but also boosts the immune response, providing a double punch against cancer.

What evidence suggests that photoimmunotherapy with ASP-1929 and cemiplimab could be effective for non-small cell lung cancer?

In this trial, participants will receive a combination treatment involving ASP-1929 and cemiplimab. Research has shown that ASP-1929, when used with a special light-based treatment called photoimmunotherapy (PIT), holds promise for treating cancer. Early results suggest it helps patients live longer and reduces tumor size. ASP-1929 combines a drug that targets cancer cells with a light-activated component to help destroy these cells.

Cemiplimab, another part of this treatment, has improved survival rates in patients with advanced non-small cell lung cancer (NSCLC). Specifically, studies have shown that patients treated with cemiplimab lived for an average of 21.1 months, compared to 12.9 months with standard chemotherapy. This combination of ASP-1929 and cemiplimab aims to boost the body's immune system to fight cancer cells more effectively. ^{1 4 6 7 8}

Who Is on the Research Team?

Prantesh Jain

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with advanced non-small cell lung cancer (stage IIIB-IV) that hasn't improved with previous treatments, can't be removed by surgery, or has spread. Participants must have tumors that express a protein called EGFR.

Inclusion Criteria

Meet specific laboratory criteria for neutrophil count, platelets, bilirubin, AST/ALT, and creatinine clearance

Understand and sign informed consent form

I am not pregnant and will use birth control.

Exclusion Criteria

I am currently pregnant or nursing.

Unable to follow protocol requirements

Received investigational agent within 30 days prior to treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab IV on days 1, 22, and 43, and ASP-1929 IV on day 8 of each cycle. External beam or interstitial photoimmunotherapy is performed on day 9 of cycles 1, 2, and/or 3. Cycles repeat every 9 weeks for up to 2 years.

Up to 2 years

Multiple visits per cycle, including IV administration and PIT procedures

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months.

Up to 2 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• ASP-1929
• Cemiplimab

Trial Overview The study tests photoimmunotherapy (PIT) using ASP-1929 combined with cemiplimab. PIT activates drugs with light to target tumor cells, while cemiplimab boosts the immune system's response against the tumor.

How Is the Trial Designed?

Group I: Treatment (photoimmunotherapy, ASP-1929, cemiplimab) Experimental Treatment 11 Interventions

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.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Rakuten Medical, Inc.

Industry Sponsor

Trials

7

Recruited

630+

Published Research Related to This Trial

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Cemiplimab, a PD-1 targeting monoclonal antibody, demonstrated an objective response rate of 45.5% in a real-life study of 33 patients with advanced cutaneous squamous cell carcinoma, confirming its efficacy as a treatment option.

The addition of radiotherapy to cemiplimab resulted in a quicker response time, with a median duration of response of 5.5 months compared to 3 months for cemiplimab alone, and did not increase adverse events, indicating a safe and effective combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study. Bailly-Caillé, B., Kottler, D., Morello, R., et al.[2023]

Cemiplimab, an anti-PD-1 monoclonal antibody, demonstrated a favorable safety profile in a study of 60 patients with advanced solid tumors, with no dose-limiting toxicities and manageable treatment-emergent adverse events like fatigue and nausea.

The treatment showed promising antitumor activity, with 2 complete responses and 7 partial responses, and responses lasting at least 12 months in some patients, indicating its potential effectiveness when combined with hypofractionated radiotherapy and/or cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Papadopoulos, KP., Johnson, ML., Lockhart, AC., et al.[2021]

At 35 months of follow-up, patients with advanced non-small-cell lung cancer and high PD-L1 expression treated with cemiplimab had a median overall survival of 26.1 months, significantly better than the 13.3 months for those receiving chemotherapy, indicating a strong survival benefit from cemiplimab.

The addition of chemotherapy to cemiplimab after disease progression resulted in a median overall survival of 15.1 months, suggesting that this combination could be an effective second-line treatment option for patients with advanced non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Özgüroğlu, M., Kilickap, S., Sezer, A., et al.[2023]

In the EMPOWER-Lung 1 trial, cemiplimab significantly improved overall survival compared to platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression (≥50%).

Patients receiving cemiplimab reported better quality of life and functioning, with a lower risk of definitive deterioration in symptoms such as dyspnea, cough, and fatigue, indicating that cemiplimab not only extends survival but also enhances the patient's overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. Gümüş, M., Chen, CI., Ivanescu, C., et al.[2023]

Cemiplimab significantly improves overall survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 levels, adding 0.546 quality-adjusted life years (QALYs) compared to chemotherapy.

The treatment is considered cost-effective, with an incremental cost-effectiveness ratio of $40,390 per QALY gained, and a 100% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50. Wang, L., Peng, Y., Zeng, X., et al.[2021]

In patients with advanced non-small-cell lung cancer (NSCLC) and high PD-L1 expression (≥50%), cemiplimab showed significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared to pembrolizumab, based on a systematic review and network meta-analysis of randomized-controlled trials.

Cemiplimab demonstrated comparable overall survival (OS) and similar safety profiles to pembrolizumab, indicating it is a viable first-line treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50. Freemantle, N., Xu, Y., Wilson, FR., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6083

Recent safety and efficacy findings from a phase 1b/2 open ... ASP-1929 PIT in combination with anti-PD-1 therapy was generally well tolerated. Initial data demonstrate promising overall survival and response rates.

2. rakuten-med.com rakuten-med.com/us/news/press-releases/2025/09/18/7922/

Press Releases The ASP-1929-381 study is a multi-regional, multi-center, randomized, open-label Phase 3 trial, designed to assess the efficacy and safety of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06699212

NCT06699212 | A Study of ASP-1929 ... This is a phase 3 multicenter, randomized study designed to evaluate the efficacy and safety of ASP-1929 photoimmunotherapy (PIT) in combination with ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/599275

Photoimmunotherapy With ASP-1929 and Cemiplimab for the ... 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.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS6122

A phase 3 randomized study of ASP-1929 ... The objective of this pivotal phase 3 study is to further evaluate the efficacy and safety of ASP-1929 PIT in combination with pembrolizumab in rHNSCC.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40852760/

Safety and Efficacy Findings From a Phase Ib/II Study of ... ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hed.70014

Safety and Efficacy Findings From a Phase Ib/II Study of ... ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC. 1 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03769506

NCT03769506 | ASP-1929 Photoimmunotherapy (PIT) ... ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/​Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy. ClinicalTrials.gov ID ...