Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Immatics US, Inc.
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.
12345Eligibility 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.
My melanoma worsened after treatment with a PD-1 inhibitor.
My melanoma cannot be removed by surgery and has spread.
My HLA type matches the study requirements.
I am using birth control and will continue for 12 months after my treatment.
I have recovered from previous treatment side effects.
Exclusion Criteria
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.
I haven't had any cancer except skin cancer or localized cancer in the last 3 years.
I had a treatment to reduce my immune cells before cell therapy in the last 6 months.
I have previously been treated with IMA203.
I have had a stem cell or organ transplant in the past.
I have a history of heart conditions.
I am HIV positive or have active hepatitis B or C.
I do not have any health issues that prevent leukapheresis.
I currently have an active infection or a reactivating infection.
I've needed frequent fluid removal from my abdomen or chest in the last 2 months.
I have taken corticosteroids within the last 2 weeks.
I am not currently participating in another clinical trial that could affect this treatment.
I have active brain or leptomeningeal metastases.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Experimental armExperimental Treatment1 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 choiceActive Control10 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
UPMC Hillman Cancer CenterPittsburgh, PA
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Who is running the clinical trial?
Immatics US, Inc.Lead Sponsor
References
Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. [2018]Imiquimod, a TLR7 agonist, is a novel immune response modifier currently widely used in the treatment of actinic keratoses (in situ squamous cell carcinoma). Imiquimod has revolutionized the treatment of field cancerization and has been approved for the treatment of superficial basal cell carcinoma with the recommendation of a 6-week treatment strategy, offering an alternative to surgery or other destructive treatment strategies.
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]Cutaneous squamous cell carcinomas are a common form of highly mutated keratinocyte skin cancers that are of particular concern in immunocompromised patients. Here we report on the efficacy of topically applied MS-275, a clinically used histone deacetylase inhibitor, for the treatment and management of this disease. At 2 mg/kg, MS-275 significantly decreased tumor burden in an SKH-1 hairless mouse model of UVB radiation-induced skin carcinogenesis. MS-275 was cell permeable as a topical formulation and induced histone acetylation changes in mouse tumor tissue. MS-275 was also effective at inhibiting the proliferation of patient derived cutaneous squamous cell carcinoma lines and was particularly potent toward cells isolated from a regional metastasis on an immunocompromised individual. Our findings support the use of alternative routes of administration for histone deacetylase inhibitors in the treatment of high-risk squamous cell carcinoma which may ultimately lead to more precise delivery and reduced systemic toxicity.
Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial. [2023]Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation.
Periocular Melanoma In Situ Treated With Imiquimod. [2023]To evaluate the efficacy of topical 5% imiquimod cream in the treatment of periocular melanoma in situ (lentigo maligna).
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]A shorter dosing regimen of imiquimod for the treatment of actinic keratosis may be effective, with long-term clinical benefits.
Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach. [2023]Label="Background" NlmCategory="UNASSIGNED">Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option.
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]Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2-30.3); diclofenac 3% 2.9 (1.9-4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6-13.5); fluorouracil 4% 30.3 (9.1-144.7); fluorouracil 5% 35.0 (10.2-164.4); imiquimod 3.75% 8.5 (3.5-22.4); imiquimod 5% 17.9 (9.1-36.6); ingenol mebutate 0.015% 12.5 (8.1-19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9-52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0-21.9); tirbanibulin 1% 11.1 (6.2-20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm2 treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.
Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients. [2018]To document the impact on patient-reported outcomes and health-related quality of life (HRQoL) of treatment with imiquimod cream in patients with actinic keratosis (AK) and superficial basal cell carcinoma (sBCC).
Topical imiquimod therapy for basal and squamous cell carcinomas: a clinical experience. [2018]Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most common malignancies in humans. Together, they constitute approximately 95% of nonmelanoma skin cancers (NMSCs). Surgical excision remains the mainstay of therapy of low-risk NMSC, though Mohs micrographic surgery is the gold standard for high-risk NMSC. Both methods produce high cure rates, but they may not be appropriate treatments for elderly patients who are either not surgical candidates or refuse to undergo surgery for their skin cancers. Imiquimod cream 5% is a topical immune response modifier that targets the toll-like receptors 7 and 8 and up-regulates inflammatory pathways targeting diseased tissue. This noninvasive topical therapy may be more appropriate for some patients. Herein, we describe our 5-month clinical experience in mostly elderly subjects with BCC (n=21) or SCC (n= 19) who were not candidates for surgical excision and were treated with topical imiquimod. Most subjects had a history of skin cancer, and the median age of the subjects was 78 years and 79 years in the BCC and SCC groups, respectively. After biopsy alone or biopsy followed by curettage, subjects received imiquimod cream 5% once daily 5 times weekly for 6 weeks. Twenty-three BCC lesions and 22 SCC lesions were included in the analysis. Most of the 45 lesions treated were located on the head and most were in high-risk areas. Approximately 3 months after imiquimod therapy, repeat biopsies showed that only 3 (2 BCCs and 1 SCC) lesion sites had residual tumor. After a median follow-up of 26 months, there was only one additional SCC recurrence. We also present a selection of representative case studies. Imiquimod cream 5% as adjunctive therapy to curettage was safe and well-tolerated in this mostly elderly population. The improved residual tumor and recurrence rates compared with historical rates for electrodesiccation and curettage (ED&C) alone suggest that adjunctive imiquimod therapy may be an appropriate treatment option for patients who desire or require less invasive treatment for NMSCs.