IMA203 for Skin Cancer

(SUPRAME Trial)

Recruiting at 11 trial locations

Overseen By Immatics US, Inc.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Immatics US, Inc.

Must not be taking: Systemic corticosteroids, Immunosuppressive agents

Disqualifiers: Other malignancies, Autoimmune disease, Cardiac conditions, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This clinical trial is a prospective, multicenter, open-label, randomized, actively controlled, parallel-group Phase 3 clinical trial to evaluate the efficacy, safety and tolerability of treatment with IMA203 administered at the recommended phase 2 dose versus investigator's choice of treatment in patients with previously treated, unresectable or metastatic cutaneous melanoma.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received systemic corticosteroids within 2 weeks before a certain procedure, or any anti-cancer therapy or radiotherapy within 1 week before starting the trial treatment.

What data supports the effectiveness of the treatment IMA203 for skin cancer?

Research shows that imiquimod, a component used in similar treatments, has been effective in treating various skin cancers, including basal cell carcinoma and melanoma, by boosting the immune response to fight cancer cells. This suggests that treatments like IMA203, which may involve similar mechanisms, could potentially be effective for skin cancer. ^{1 2 3 4 5}

Is IMA203 safe for treating skin cancer?

The treatment imiquimod, which may be related to IMA203, has been used safely in humans for skin conditions like basal cell carcinoma and actinic keratosis. It is generally well-tolerated, though it can cause local skin reactions. ^{1 6 7 8 9}

Research Team

Cedrik Britten, M.D.

Principal Investigator

Immatics US, Inc.

Eligibility Criteria

This trial is for adults with confirmed cutaneous melanoma that's spread and can't be removed by surgery. They must have tried a PD-1 inhibitor treatment before, have good organ function, and an ECOG status of 0-1 (which means they're fully active or restricted in physically strenuous activity but can do light work). Women who can have children and men must agree to use contraception.

Inclusion Criteria

I am fully active or can carry out light work.

Life expectancy more than 6 months

My HLA type matches the study requirements.

Exclusion Criteria

Known hypersensitivity to any of the rescue medications

I am not allergic to CY, FLU, or IL-2 and have no contraindications for the planned treatment.

My melanoma originates from mucosal surfaces, the eye, or its primary location is unknown.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Manufacturing

IMA203 products will be made from the patients' white blood cells

2-4 weeks

Treatment

Lymphodepletion with cyclophosphamide and fludarabine followed by IMA203 infusion and low dose IL-2 for up to 10 days

2 weeks

Hospital admission for T-cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Regular visits, can include phone assessments

Treatment Details

Interventions

• IMA203 (Cancer Vaccine)

Trial Overview The trial tests IMA203 against the investigator's choice from treatments like chemotherapy drugs paclitaxel plus carboplatin, immunotherapies pembrolizumab or ipilimumab, among others. It's randomized and open-label, meaning patients know which treatment they receive. The goal is to compare effectiveness and safety.

Participant Groups

Group I: Experimental arm Experimental Treatment 1 Intervention

Non-myeloablative chemotherapy for lymphodepletion (LD) over 4 days using fludarabine (FLU) and cyclophosphamide (CY), one-time administration of IMA203, and adjunctive therapy with low dose interleukin (IL)-2 for up to 10 days, starting approximately 24 h after IMA203 infusion, optional bridging therapy

Group II: Control arm- investigator's choice Active Control 10 Interventions

Investigator's choice of treatment approved by the respective Competent Authority (nivolumab plus relatlimab \[Opdualag®\], lifileucel, nivolumab, pembrolizumab, ipilimumab, or chemotherapy \[e.g., dacarbazine, temozolomide, paclitaxel, alb-bound paclitaxel, or paclitaxel plus carboplatin\]) as determined by the site investigator in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC), optional bridging therapy.

Who Is Running the Clinical Trial?

Immatics US, Inc.

Lead Sponsor

Trials

6

Recruited

1,100+

Findings from Research

Imiquimod is an effective TLR7 agonist that modifies the immune response and is currently used to treat actinic keratoses and superficial basal cell carcinoma.

The treatment regimen for superficial basal cell carcinoma involves a 6-week application of imiquimod, providing a non-surgical alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. Papakostas, D., Stockfleth, E.[2018]

Topically applied MS-275, a histone deacetylase inhibitor, significantly reduced tumor burden in a mouse model of skin cancer, indicating its potential efficacy for treating cutaneous squamous cell carcinomas, especially in immunocompromised patients.

MS-275 was effective in inhibiting the growth of patient-derived cancer cells, particularly those from a metastatic site, suggesting that this treatment could be a targeted option for high-risk cases with reduced systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model. Kalin, JH., Eroglu, A., Liu, H., et al.[2023]

In a study of 25 stage III-IV melanoma patients treated with a combination of monobenzone and imiquimod for 12 weeks, 38% showed local regression of cutaneous metastases, indicating the treatment's efficacy.

The therapy was well-tolerated and induced systemic immune responses, including melanoma-specific antibodies and CD8+ T-cell responses, suggesting it may enhance the body's overall anti-melanoma immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial. Teulings, HE., Tjin, EPM., Willemsen, KJ., et al.[2023]

In a study of 12 patients with periocular melanoma in situ, topical 5% imiquimod cream led to complete histologic clearance of atypical melanocytes in 11 patients after a mean treatment duration of 3.9 months, demonstrating its efficacy as a treatment option.

While most patients experienced mild side effects like redness and discomfort, there were no systemic side effects, indicating that imiquimod cream is a safe local treatment for this type of skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periocular Melanoma In Situ Treated With Imiquimod. Elia, MD., Lally, SE., Hanlon, AM., et al.[2023]

Imiquimod applied three times a week for one or two shorter treatment courses resulted in a complete clearance rate of 26.8% after the first course and 53.7% overall, indicating its effectiveness in treating actinic keratosis.

After one year, recurrence rates were 39% for those treated with imiquimod, suggesting that while the treatment is effective, long-term follow-up is necessary due to the possibility of lesions returning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. Jorizzo, J., Dinehart, S., Matheson, R., et al.[2018]

The study developed nanostructured lipid carriers (NLCs) for imiquimod (IMQ), which significantly improved the drug's deposition in deeper skin layers compared to the commercial cream, enhancing its potential efficacy for treating skin conditions.

The optimized IMQ-NLC formulation was incorporated into a matrix-type patch, which not only improved drug delivery but also aimed to be more patient-friendly and environmentally sustainable, addressing common issues with topical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach. Kim, S., Abdella, S., Abid, F., et al.[2023]

Tirbanibulin 1% ointment is an effective new treatment for actinic keratosis (AK), showing similar efficacy to established treatments like fluorouracil and photodynamic therapy, with an odds ratio of 11.1 for complete clearance.

The systematic review included 46 studies and confirmed that tirbanibulin has a favorable safety profile and can be applied in a single short treatment period, making it a convenient option for patients compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Heppt, MV., Dykukha, I., Graziadio, S., et al.[2022]

In a study involving 202 patients (118 with actinic keratosis and 84 with superficial basal cell carcinoma), treatment with imiquimod 5% cream showed no significant negative impact on health-related quality of life (HRQoL) as measured by the Skindex-17 and Skin Cancer Index.

While there was a slight dip in HRQoL at the end of the treatment period, overall, the findings suggest that imiquimod treatment does not lead to clinically relevant changes in patients' quality of life, indicating its safety in this regard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients. Waalboer-Spuij, R., Holterhues, C., van Hattem, S., et al.[2018]

In a study involving 40 elderly patients (median age 78-79) with nonmelanoma skin cancers (BCC and SCC) who were not candidates for surgery, treatment with imiquimod cream 5% showed promising results, with only 3 out of 45 lesions having residual tumors after therapy.

Imiquimod was found to be safe and well-tolerated, and its use as an adjunctive therapy led to improved tumor control compared to traditional methods like electrodesiccation and curettage, suggesting it may be a suitable noninvasive option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical imiquimod therapy for basal and squamous cell carcinomas: a clinical experience. Tillman, DK., Carroll, MT.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. [2018]

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

Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model. [2023]

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

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial. [2023]

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

Periocular Melanoma In Situ Treated With Imiquimod. [2023]

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

Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients. [2018]

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

Topical imiquimod therapy for basal and squamous cell carcinomas: a clinical experience. [2018]