IMA203 for Skin Cancer

(SUPRAME Trial)

Recruiting at 44 trial locations

Overseen By Immatics US, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Immatics US, Inc.

Must not be taking: Systemic corticosteroids, Immunosuppressive agents

Disqualifiers: Other malignancies, Autoimmune disease, Cardiac conditions, 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: 1

Duration: 2 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called IMA203 for individuals with skin cancer that has spread or cannot be surgically removed. It compares IMA203 to other treatments selected by doctors to determine which better controls the cancer. The trial seeks participants with skin cancer that has worsened after at least one other treatment and who have a specific genetic marker (HLA-A*02:01 positive). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that IMA203 is likely to be safe for humans?

Research has shown that IMA203, a cell therapy for skin cancer, is generally well tolerated. In earlier studies, patients demonstrated a consistent and positive safety record, with most side effects being minor. The treatment also produced encouraging results, with more than half of the patients responding positively. Although side effects can occur, evidence suggests that IMA203 is safe for individuals when administered as part of a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, such as nivolumab or pembrolizumab, IMA203 is unique because it targets specific cancer cells through a novel approach. IMA203 is a type of personalized immunotherapy that uses non-myeloablative chemotherapy for lymphodepletion, followed by a one-time administration of IMA203, and then adjunctive therapy with low-dose interleukin-2. This combination aims to enhance the body's immune response against cancer cells more effectively. Researchers are excited about IMA203 because it has the potential to improve outcomes by focusing on precision targeting, offering a new way to potentially boost the effectiveness of treatment against skin cancer.

What evidence suggests that IMA203 might be an effective treatment for skin cancer?

Research has shown that IMA203, which participants in this trial may receive, effectively treats melanoma, a type of skin cancer. It reduced tumor size in 85% of patients and controlled the disease in 92% of cases. On average, the disease remained stable for about 6.1 months, and patients lived for an average of 15.9 months. In patients with cutaneous melanoma, IMA203 demonstrated a 54% overall response rate. These results suggest that IMA203 could be a promising treatment option for people with melanoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Cedrik Britten, M.D.

Principal Investigator

Immatics US, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IMA203

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

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investors.immatics.com

investors.immatics.com/news-releases/news-release-details/immatics-ima203-prame-cell-therapy-data-presented-2025-asco-0

Immatics IMA203 PRAME Cell Therapy Data Presented at ...

Translational analyses demonstrated that treatment with IMA203 resulted in the shrinkage of metastatic target lesions throughout the body. This ...

2.

onclive.com

onclive.com/view/ima203-displays-efficacy-in-heavily-pretreated-melanoma

IMA203 Displays Efficacy in Heavily Pretreated Melanoma

The disease control and tumor shrinkage rates were 92% and 85%, respectively. The median PFS was 6.1 months, and the median OS was 15.9 months.

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2673

SUPRAME: A phase 3 trial comparing IMA203 ...

IMA203 TCR-T demonstrated a favorable tolerability profile and durable objective responses in heavily-pretreated patients with different tumor ...

4.

cancernetwork.com

cancernetwork.com/view/ima203-shows-frequent-enduring-responses-and-tolerability-in-melanoma

IMA203 Shows Frequent, Enduring Responses and ...

IMA203 produced a confirmed overall response rate (ORR) of 54% and 60% among patients with cutaneous (n = 13) and uveal melanoma (n = 10), respectively.

5.

targetedonc.com

targetedonc.com/view/promising-results-for-ima203-in-targeted-oncology-a-prame-targeted-trial

Promising Results for IMA203 in Melanoma: A PRAME ...

IMA203 showed an excellent safety profile and promising efficacy in solid tumors, leading to a new registration-directed clinical trial.

6.

dailynews.ascopubs.org

dailynews.ascopubs.org/do/autologous-t-cell-receptor-therapy-ima203-displays-safety-high-activity-phase-1

Autologous T-Cell Receptor Therapy IMA203 Displays ...

IMA203, an autologous T-cell receptor therapy (TCR-T) targeting the intracellular protein PRAME, was generally well tolerated and showed promising activity in ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06743126

NCT06743126 | SUPRAME-ACTengine® IMA203 vs. ...

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (SUPRAME). ClinicalTrials.

8.

investors.immatics.com

investors.immatics.com/static-files/0c1b2d89-79ee-489c-82d7-b474b57ab0a2

Efficacy and Safety of Anzutresgene Autoleucel (IMA203)

Cutaneous melanoma. 95%. Uterine carcinoma. 95%. Uterine carcinosarcoma. 95%. Synovial sarcoma. 95%. Uveal melanoma2. 90%. Mucosal melanoma. 90 ...

9.

onclive.com

onclive.com/view/suprame-trial-seeks-to-establish-ima203-as-the-first-tcr-based-therapy-for-cutaneous-melanoma

SUPRAME Trial Seeks to Establish IMA203 as the First ...

The phase 3 SUPRAME trial is comparing IMA203 vs investigator's choice of therapy in patients with pretreated unresectable or metastatic cutaneous melanoma.