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

27 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug ASP-1929, Cemiplimab, for lung cancer?

Research shows that cemiplimab, when used alone, significantly improves survival in patients with advanced non-small cell lung cancer with high PD-L1 levels compared to traditional chemotherapy. ^{1 2 3 4 5}

Is cemiplimab safe for use in humans?

Cemiplimab, used in treating advanced cancers, has a safety profile similar to other treatments targeting the PD-1 receptor, but it can cause serious side effects like pneumonitis (lung inflammation). ^{1 3 6 7 8}

How is the treatment ASP-1929, Cemiplimab unique for lung cancer?

This treatment combines photoimmunotherapy, which uses light to activate a drug that targets cancer cells, with cemiplimab, a drug that helps the immune system attack cancer by blocking a protein called PD-1. This combination is unique because it uses both light-activated therapy and immune system activation to target lung cancer. ^{1 2 5 9 10}

What is the purpose of this trial?

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.

Research Team

Prantesh Jain

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. United States 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. [2023]

3. England 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. [2022]

4. England 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. [2023]

5. United States 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic characteristics of cemiplimab in patients with advanced malignancies. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Dynamic changes in the radiologic manifestation of a recurrent checkpoint inhibitor related pneumonitis in a non-small cell lung cancer patient: A case report. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies. [2023]

9. Switzerland 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. [2023]

10. United States 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. [2021]