Padeliporfin VTP for Lung Cancer

Overseen By Eyal Morag, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Impact Biotech Ltd

Must not be taking: Anticoagulants, Antiplatelets, Antibiotics, others

Disqualifiers: Pregnancy, Heart failure, Hypoxia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1/1b, safety, feasibility, and light dose titration study followed by further study of therapeutic ablation effects. Patients with high risk of peripheral primary lung cancer, stage 1A1/1A2, for whom surgical treatment is planned, will be recruited. Surgery will be performed at 5-21 days following the VTP procedure. Study intervention: robotic assisted bronchoscopic Padeliporfin VTP lung ablation: vascular targeted photodynamic therapy using Padeliporfin photosensitizer.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to stop anticoagulation or anti-platelet therapy around the time of the procedure.

What data supports the effectiveness of the treatment Padeliporfin VTP for lung cancer?

Padeliporfin VTP has shown promise in treating localized prostate cancer and upper tract urothelial carcinoma by targeting blood vessels in tumors, which suggests it might be effective for other cancers like lung cancer. This treatment uses a special light-activated drug to destroy cancer cells, and its success in other cancers provides hope for its potential use in lung cancer. ^{1 2 3 4 5}

Is Padeliporfin VTP safe for use in humans?

Padeliporfin VTP has been evaluated for safety in clinical trials for localized prostate cancer and upper tract urothelial carcinoma, showing it to be a minimally invasive treatment with a focus on safety and quality of life. While specific safety data for lung cancer is not available, its use in other conditions suggests it is generally safe in humans. ^{1 2 4 5 6}

What makes the drug Padeliporfin VTP unique for treating lung cancer?

Padeliporfin VTP is unique because it uses a light-activated process called photodynamic therapy, which targets cancer cells with a special drug that becomes active when exposed to light, causing the cancer cells to die. This approach is different from traditional treatments like chemotherapy, which affect both cancerous and healthy cells. ^{7 8 9 10 11}

Research Team

Lonny Yarmus, DO

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults with early-stage peripheral lung cancer, who are high-risk surgical candidates. Eligible patients must have a tumor ≤3cm based on CT scans and confirmed malignancy via biopsy. The tumor should be accessible by robotic bronchoscopy, not too close to the central airways or pleura, and without nodal involvement of cancer.

Inclusion Criteria

I am at high risk for lung cancer due to a primary lung lesion.

My cancer was confirmed malignant with a biopsy during surgery.

A team of lung cancer specialists has approved me for a specific lung procedure before surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Robotic assisted bronchoscopic Padeliporfin VTP lung ablation with light dose escalation to determine MTD/RP2D

1 day

1 visit (in-person)

Surgery

Surgery performed 5-21 days following the VTP procedure to assess feasibility and safety

5-21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of treatment-related adverse events

30 days

Treatment Details

Interventions

• Padeliporfin VTP

Trial Overview The study tests Padeliporfin Vascular Targeted Photodynamic (VTP) therapy using robotic-assisted bronchoscopy in patients with peripheral lung tumors. It's a Phase 1/1b trial focusing on safety and optimal light dose before surgery scheduled within 5-21 days post-VTP.

Participant Groups

Group I: Part B Experimental Treatment 1 Intervention

will be a dose expansion part at MTD/RP2D dose level identified in Part A to further assess the safety, tolerability, and treatment effect of the MTD and/ or RP2D

Group II: Part A Experimental Treatment 1 Intervention

will be a monotherapy light dose escalation with single dose of Padeliporfin at light laser doses of 150, 250 and 400 mW/cm for 20 minutes. Part A will proceed with light dose escalation and will continue until the maximum tolerated light dose (MTD) and/or recommended phase 2 dose (RP2D) is defined.

Padeliporfin VTP is already approved in European Union for the following indications:

Approved in European Union as Tookad for:

• Low-risk prostate cancer
• Upper tract urothelial carcinoma (UTUC)

Who Is Running the Clinical Trial?

Impact Biotech Ltd

Lead Sponsor

Trials

2

Recruited

70+

Steba Biotech S.A.

Lead Sponsor

Trials

17

Recruited

1,300+

Impact biotech Ltd.

Collaborator

Trials

2

Recruited

70+

Findings from Research

Vascular targeted photochemotherapy (VTP) using padoporfin and padeliporfin is a promising, minimally invasive treatment for localized prostate cancer, allowing for outpatient procedures.

Clinical trials indicate that VTP is effective for focal treatment of prostate cancer, and future developments aim to standardize this method with real-time feedback protocols and cost-effectiveness analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. Bugaj, AM.[2020]

In a Phase I trial involving 19 patients with upper tract urothelial carcinoma, vascular-targeted photodynamic therapy using the agent WST-11 showed a high initial treatment response rate of 94%, with 50% achieving complete response and 44% partial response within 30 days.

The therapy demonstrated an acceptable safety profile, with transient side effects like flank pain and hematuria, and no significant long-term complications such as ureteral strictures, indicating its potential as a kidney-sparing treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma. Yip, W., Sjoberg, DD., Nogueira, LM., et al.[2023]

Photodynamic therapy (PDT) is gaining renewed interest in treating urological cancers due to advancements in understanding cancer biology and the development of better photosensitizers.

Vascular-targeted PDT (VTP) using padeliporfin has shown tumor-specific effectiveness, making it a promising option for managing urologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. Nogueira, L., Tracey, AT., Alvim, R., et al.[2021]

In a study of 86 men with localized prostate cancer, treatment with 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light resulted in 83% of patients having negative biopsy results for cancer at 6 months, indicating high efficacy for this treatment regimen.

The treatment was well tolerated, with most adverse events being mild or moderate, and no serious complications leading to discontinuation, suggesting that TOOKAD(®) Soluble VTP is a safe option for minimally invasive prostate cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. Azzouzi, AR., Barret, E., Moore, CM., et al.[2014]

Verteporfin (VP), traditionally used for treating age-related macular degeneration through photodynamic therapy, has shown significant anti-tumor effects by inhibiting the pro-tumorigenic factor YAP, which is involved in various cancers.

VP can exert its anti-cancer effects both with and without light activation, making it a promising candidate for repositioning as an anti-cancer chemotherapeutic and adjuvant drug, due to its ability to induce mitochondrial damage and increase reactive oxygen species production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor. Wei, C., Li, X.[2020]

The study evaluated 5,10,15,20-tetra(quinolin-2-yl)porphyrin (2-TQP) as a potential photosensitizer for photodynamic therapy (PDT), finding it to have a high quantum yield of singlet oxygen generation (Φ∆ 0.62), which is crucial for effectively destroying cancer cells.

2-TQP demonstrated significant in vitro phototoxicity against HT29 colorectal adenocarcinoma cells without causing dark toxicity, indicating its potential as a safe and effective PDT agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for Photodynamic Therapy. Costa, LD., e Silva, Jde A., Fonseca, SM., et al.[2020]

The cationic porphyrin T4MPyP demonstrated strong tumor localization in Balb/c mice with fibrosarcoma, achieving a concentration of approximately 1.2 ng/mg in tumors 24 hours post-administration, while levels in normal tissues were significantly lower.

Photodynamic therapy (PDT) using T4MPyP resulted in a temporary delay in tumor growth when irradiated, indicating its potential effectiveness as a treatment option in photodynamic therapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and tumour-photosensitizing properties of the cationic porphyrin meso-tetra(4N-methylpyridyl)porphine. Villanueva, A., Jori, G.[2019]

The study identified a promising water-soluble porphyrin-platinum complex that combines the effects of cisplatin and photodynamic therapy, showing enhanced cytotoxicity against bladder cancer cells compared to traditional treatments.

This compound demonstrated a synergistic effect, meaning it worked better together than the individual drugs alone, suggesting a new potential strategy for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates. Lottner, C., Knuechel, R., Bernhardt, G., et al.[2019]

The study presents a new method for synthesizing various lipophilic cationic porphyrins that contain phosphorus and nitrogen, which could be important for developing new treatments.

In vitro tests showed that these compounds have varying levels of photodynamic activity against human colorectal adenocarcinoma cells (HT-29), indicating that the chemical structure significantly influences their effectiveness in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipophilic cationic porphyrins as photodynamic sensitisers-Synthesis and structure-activity relationships. Hudson, R., Savoie, H., Boyle, RW.[2014]

The study found that palladium(II)-tetraphenylporphycene (PdTPP(0)) effectively kills HeLa cancer cells when activated by red light, showing no toxicity in the dark, which suggests a safe application for photodynamic therapy.

PdTPP(0) demonstrated superior photokilling properties compared to its predecessor, tetraphenylporphycene (TPP(0)), indicating its potential as a more effective sensitizer for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photosensitizing properties of palladium-tetraphenylporphycene on cultured tumour cells. Cañete, M., Ortiz, A., Juarranz, A., et al.[2006]

Palladium(II)-tetraphenylporphycene (PdTPPo) showed no dark toxicity in human lung adenocarcinoma A-549 cells at low concentrations, but induced dose-dependent necrotic cell death when combined with red light irradiation.

The study found that the mechanism of cell death in A-549 cells was primarily necrosis rather than apoptosis, highlighting the importance of cell type in determining the response to photodynamic therapy and indicating that cytoskeletal components are key targets in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Necrotic cell death induced by photodynamic treatment of human lung adenocarcinoma A-549 cells with palladium(II)-tetraphenylporphycene. Cañete, M., Ortega, C., Gavaldá, A., et al.[2019]

References

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

Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. [2020]

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

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. [2021]

4. England pubmed.ncbi.nlm.nih.gov

TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. [2014]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for Photodynamic Therapy. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and tumour-photosensitizing properties of the cationic porphyrin meso-tetra(4N-methylpyridyl)porphine. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Lipophilic cationic porphyrins as photodynamic sensitisers-Synthesis and structure-activity relationships. [2014]

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

Photosensitizing properties of palladium-tetraphenylporphycene on cultured tumour cells. [2006]

11. Greece pubmed.ncbi.nlm.nih.gov

Necrotic cell death induced by photodynamic treatment of human lung adenocarcinoma A-549 cells with palladium(II)-tetraphenylporphycene. [2019]