Belzupacap Sarotalocan for Eye Melanoma

(CoMpass Trial)

Recruiting at 84 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called belzupacap sarotalocan (bel-sar) to determine its safety and effectiveness for eye conditions like primary indeterminate lesions or small choroidal melanoma. Researchers aim to assess whether bel-sar, when used with a laser, outperforms a sham treatment. Participants are divided into two groups receiving different doses of bel-sar, along with a control group receiving a sham treatment. Individuals who have not previously received treatment for these eye conditions and show no signs of cancer spread may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

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.

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

Research has shown that belzupacap sarotalocan, when combined with a laser, is generally safe according to previous studies. No serious side effects related to the drug or the laser have been reported so far. Any side effects that occurred were mild, such as minor irritation or discomfort.

The treatment targets and destroys cancer cells specifically, potentially sparing healthy cells. This could result in fewer side effects. These findings suggest that belzupacap sarotalocan is generally well-tolerated, making it a potential option for those considering clinical trials for eye melanoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for eye melanoma, which often involve surgery, radiation, or chemotherapy, Belzupacap Sarotalocan offers a novel approach by combining a targeted drug with laser application. This investigational treatment is unique because it uses an innovative active ingredient that specifically targets cancer cells in the eye. Researchers are excited about this approach due to its potential for precision, minimizing damage to surrounding healthy tissue. Additionally, the combination of the drug with laser therapy may enhance the effectiveness of the treatment, offering a promising new avenue for patients facing this challenging condition.

What evidence suggests that this trial's treatments could be effective for eye melanoma?

Research has shown that belzupacap sarotalocan, when combined with a laser, may effectively treat eye melanoma. In this trial, participants will receive either a low or high dose of belzupacap sarotalocan with laser application, or they will join a sham control arm with a sham laser. Early studies indicate that 88-90% of patients retain their vision, meaning most people maintain their eyesight. This treatment activates with light and specifically targets melanoma cells, potentially protecting the surrounding healthy tissue. Initial results suggest it might preserve vision better than traditional treatments like radiation. These encouraging findings support the potential of bel-sar in managing small choroidal melanoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Monitor

Principal Investigator

Aura Biosciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06007690

Study Details | NCT06007690 | A Phase 3 Randomized, ... A Phase 3 Randomized, Masked, Controlled Trial to Evaluate Efficacy and Safety of Belzupacap Sarotalocan (AU-011) Treatment Compared to Sham Control in Subjects ...

2. aurabiosciences.com aurabiosciences.com/wp-content/uploads/2023/02/Macula-Society-2023-SC-Administration-2022_02_16_FINAL-as-presented.pdf

A Phase 2 Trial of Belzupacap Sarotalocan (AU-011) Initial safety and efficacy data in this ongoing Ph2 trial support SC administration as a potential route. Visual acuity preservation rate of 88-90% even in ...

3. aurabiosciences.com aurabiosciences.com/companynews/aura-biosciences-announces-interim-phase-1b-2-data-on-light-activated-au-011-for-primary-ocular-melanoma/

Aura Biosciences Announces Interim Phase 1b/2 Data on ... AU-011 is a first-in-class targeted therapy in development for the primary treatment of ocular melanoma, also known as uveal or choroidal melanoma, a rare and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2667376224000726

Targeting ocular malignancies using a novel light-activated ... These pre-clinical and clinical trials show the effectiveness and safety of Bel-sar as first-line treatment of small choroidal melanoma and indeterminate ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10712974/

Outcomes after Proton Beam Irradiation in Patients with ... Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.

6. ir.aurabiosciences.com ir.aurabiosciences.com/news-releases/news-release-details/aura-biosciences-present-phase-2-safety-data-evaluating

Aura Biosciences to Present Phase 2 Safety Data ... Belzupacap sarotalocan selectively targets and destroys cancer cells and activates the immune system with the potential to create long-lasting ...

7. chiesiventures.com chiesiventures.com/aura-biosciences-announces-positive-interim-phase-2-safety-and-efficacy-data-of-belzupacap-sarotalocan-bel-sar-for-the-first-line-treatment-of-patients-with-early-stage-choroidal-melanoma-with-supra/

Aura Biosciences Announces Positive Interim Phase 2 ... These latest results strongly support the potential of bel-sar to be used as a first line treatment option for patients with early-stage choroidal melanoma.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02819-8/fulltext

842P A phase II trial of AU-011, an investigational, virus ... AU-011 (belzupacap sarotalocan) is a virus-like drug conjugate (VDC) currently being investigated as a potential first-line vision-sparing treatment.