ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors

Study Overview
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Brief Summary
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The study purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Detailed Description
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SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening and a biopsy (or collection of archival tumor tissue) for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of an IMA203 or an IMA203CD8 product. MANUFACTURING: IMA203 and IMA203CD8 products will be made from the patients' white blood cells. TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203/IMA203CD8 product infusion to improve the duration of time that IMA203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion. After the IMA203/IMA203CD8 product infusion, a low dose of IL-2 will be given subcutaneously daily for 10 days. In Extension Cohort B (IMA203) nivolumab will be administered intravenously. Patients will be monitored closely throughout the study. The follow-up phase ends 5 years post infusion.

Official Title
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Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab in Patients With Recurrent and/or Refractory Solid Tumors

Conditions
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Refractory Cancer, Recurrent Cancer, Solid Tumor, Adult, Cancer

Intervention / Treatment
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* Biological: IMA203 Product
* Biological: IMA203CD8 Product
* Device: IMADetect®
* Drug: nivolumab (Opdivo®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have recurrent/progressing and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatment. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 HLA phenotype positive for the study Measurable disease according to RECIST 1.1 Adequate selected organ function per protocol Patient's tumor must express tumor antigen by IMADetect® RT-qPCR Life expectancy more than 3 months Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203/IMA203CD8 Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203/IMA203CD8 The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to lymphodepletion. Exclusion Criteria: History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years Pregnant or breastfeeding Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents. History of cardiac conditions as per protocol Prior stem cell transplantation or solid organ transplantation Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with LDH greater than 2.5-fold ULN. Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment Patients with active brain metastases Concurrent treatment in another clinical trial. For nivolumab treatment, patients must not have a history of severe immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.). Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation A<br>Dose escalation of IMA203 | Biological: IMA203 Product<br>* The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.<br>Device: IMADetect®<br>* IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.<br>|
| Experimental: Extension Cohort A<br>IMA203 at RP2D | Biological: IMA203 Product<br>* The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.<br>Device: IMADetect®<br>* IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.<br>|
| Experimental: Extension Cohort B<br>IMA203 at RP2D + nivolumab | Biological: IMA203 Product<br>* The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.<br>Device: IMADetect®<br>* IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.<br>Drug: nivolumab (Opdivo®)<br>* Nivolumab will be given post IMA203 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.<br>* Other names: Opdivo®;|
| Experimental: Extension Cohort C<br>IMA203CD8 at provisional RP2D | Biological: IMA203CD8 Product<br>* The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.<br>Device: IMADetect®<br>* IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.<br>|
| Experimental: Dose Escalation B<br>Dose escalation of IMA203CD8 | Biological: IMA203CD8 Product<br>* The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.<br>Device: IMADetect®<br>* IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials. IMADetect® is intended for investigational use only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability of treatment with treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab | Treatment emergent adverse events | 35 days | 
| Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8 | Number of patients with dose-limiting toxicities (DLTs) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of T-cells | Measurement of TCR-engineered T cells in peripheral blood | up to 5 years post treatment | 
| Tumor response | Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | up to 12 months | 
| Tumor response | Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST) | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Carcinoma, T-cell therapy, immunotherapy, Melanoma (Skin), Melanoma, Uveal, Uterine Carcinoma, Uterine Carcinosarcoma, Immatics