Belzupacap Sarotalocan for Eye Melanoma

(CoMpass Trial)

Recruiting at 65 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Aura Biosciences

Disqualifiers: Ocular infection, Metastatic disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 65 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and effectiveness of bel-sar, a drug injected into the eye and activated by a laser, in patients with specific eye conditions like IL or small CM.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Belzupacap Sarotalocan (AU-011) for treating eye melanoma?

Research shows that Belzupacap Sarotalocan (AU-011) can specifically target tumor cells in eye melanoma, leading to tumor cell death and potentially triggering an immune response against the cancer. In animal studies, AU-011 combined with immune checkpoint inhibitors resulted in long-term tumor regression and protection against new tumors, suggesting its effectiveness in treating eye melanoma. ^{1 2 3 4 5}

What makes the drug Belzupacap Sarotalocan unique for treating eye melanoma?

Belzupacap Sarotalocan is unique because it uses a virus-like particle that targets tumor cells and is activated by near-infrared light, leading to rapid tumor cell death and stimulating the immune system to fight cancer. This approach may avoid complications associated with traditional treatments like radiotherapy, which can damage nearby healthy tissues. ^{1 2 3 4 5}

Research Team

Medical Monitor

Principal Investigator

Aura Biosciences

Eligibility Criteria

This trial is for individuals with a clinical diagnosis of primary indeterminate lesions or small choroidal melanoma, who haven't had treatment for these conditions yet (except possibly PDT), and have no signs of the cancer spreading elsewhere in the body.

Inclusion Criteria

I have been diagnosed with a small eye melanoma or an uncertain eye lesion.

I haven't received treatment for my condition, except possibly PDT.

My scans show no signs of cancer spread.

Exclusion Criteria

Have known contraindications or sensitivities to the study drug or laser

I have an active eye infection or disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belzupacap sarotalocan (bel-sar) treatment via suprachoroidal administration with laser photoactivation, or sham control

65 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Belzupacap Sarotalocan
• Infrared Laser
• Sham Infrared Laser
• Sham Microinjector
• Sham Treatment
• Suprachoroidal Microinjector

Trial Overview The study is testing the safety and effectiveness of a new treatment called belzupacap sarotalocan using a special microinjector and infrared laser. Participants will be randomly assigned to either receive this new treatment or a sham (fake) procedure that mimics it without any active drug.

Participant Groups

Group I: Low dose bel-sar treatment arm & laser application Experimental Treatment 3 Interventions

Low dose of bel-sar + laser application

Group II: High dose bel-sar treatment arm & laser application Experimental Treatment 3 Interventions

High dose of bel-sar + laser application

Group III: Sham control arm & sham laser Placebo Group 2 Interventions

Sham injection + sham laser

Who Is Running the Clinical Trial?

Aura Biosciences

Lead Sponsor

Trials

7

Recruited

730+

Findings from Research

The drug belzupacap sarotalocan (AU-011) effectively induces immunogenic cell death in primary and metastatic uveal melanoma (UM) cell lines at very low concentrations (picomolar range), suggesting its potential as a targeted treatment.

AU-011 treatment was more effective in BAP1-positive UM cell lines, showing lower half-maximal effective concentration (EC50) values and higher exposure of damage-associated molecular patterns (DAMPs), which may enhance systemic immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Testing of the Virus-Like Drug Conjugate Belzupacap Sarotalocan (AU-011) on Uveal Melanoma Suggests BAP1-Related Immunostimulatory Capacity. Ma, S., Huis In't Veld, RV., Houy, A., et al.[2023]

The drug belzupacap sarotalocan (AU-011) effectively kills tumor cells and induces long-term antitumor immunity in a mouse model, with about 50% of treated animals showing tumor regression after a single treatment followed by near-infrared light activation.

Combining AU-011 with immune checkpoint inhibitors like anti-CTLA-4 or anti-PD-1 significantly enhances its effectiveness, achieving a complete response rate of 70% to 100% and providing durable protection against secondary tumors for up to 100 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-Like Particle-Drug Conjugates Induce Protective, Long-lasting Adaptive Antitumor Immunity in the Absence of Specifically Targeted Tumor Antigens. Kines, RC., Thompson, CD., Spring, S., et al.[2022]

In a study of 222 patients treated with proton beam irradiation (PBI) for small choroidal melanoma, over half experienced significant visual acuity loss (to 20/80 or worse) within 5 years, especially if tumors were near the optic disc or fovea.

The low rates of tumor recurrence (1.4%), neovascular glaucoma (4.5%), and eye loss (2.7%) suggest that while PBI is effective in controlling the tumor, it may not adequately preserve vision, highlighting the potential benefit of the investigational drug AU-011 for better vision outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment. Wu, F., Lane, AM., Trofimov, A., et al.[2023]

AU-011, a novel drug conjugate targeting uveal melanoma, shows potent anticancer activity both in vitro and in vivo, with its effectiveness linked to its ability to bind specifically to tumor cells via heparan sulfate proteoglycans (HSPG).

In rabbit models, AU-011 demonstrated significant tumor reduction after photoactivation while sparing surrounding healthy tissues, suggesting it could be a safe and effective treatment option for early-stage uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Infrared Dye-Conjugated Virus-like Particle for the Treatment of Primary Uveal Melanoma. Kines, RC., Varsavsky, I., Choudhary, S., et al.[2021]

AU-011, a new virus-like drug conjugate, effectively induces necrotic cell death and triggers a strong anti-tumor immune response, making it a promising treatment for small choroidal melanoma and potentially distant tumors.

Combining AU-011 with checkpoint blockade antibodies, particularly anti-PD-L1 and anti-LAG-3, significantly enhances treatment efficacy, achieving complete tumor responses in about 75% of mice with established tumors, indicating its potential for broader cancer therapy applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate induces complete responses in a murine model of local and distant tumors. Huis In 't Veld, RV., Ma, S., Kines, RC., et al.[2023]

References

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

In Vitro Testing of the Virus-Like Drug Conjugate Belzupacap Sarotalocan (AU-011) on Uveal Melanoma Suggests BAP1-Related Immunostimulatory Capacity. [2023]

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

Virus-Like Particle-Drug Conjugates Induce Protective, Long-lasting Adaptive Antitumor Immunity in the Absence of Specifically Targeted Tumor Antigens. [2022]

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

Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment. [2023]

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

An Infrared Dye-Conjugated Virus-like Particle for the Treatment of Primary Uveal Melanoma. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate induces complete responses in a murine model of local and distant tumors. [2023]