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JOURNAL ONKOLOGIE – STUDIE

ACTengine TCR-engineered T Cells in Solid Tumors

Rekrutierend

NCT-Nummer:
NCT03686124

Studienbeginn:
Mai 2019

Letztes Update:
07.09.2020

Wirkstoff:
IMA203 Product, Atezolizumab

Indikation (Clinical Trials):
Recurrence

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Immatics US, Inc.

Collaborator:
-

Studienleiter

Apostolia Tsimberidou, M.D., Ph.D.
Principal Investigator
MDACC, Houston, TX
Cedrik Britten, M.D.
Study Director
Immatics US, Inc.

Kontakt

Studienlocations (3 von 6)

Onkologisches Zentrum Universitätsklinikum Würzburg
Josef-Schneider-Straße 6
97080 Würzburg
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Ansprechpartner:

Phone: +49 931 201 0


Phone: +49 931 201 40953
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Studien-Informationen

Detailed Description:

SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) screening and a biopsy for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of the IMA203 product.

MANUFACTURING: IMA203 product will be made from the patient's white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203 product infusion to improve the duration of time that IMA203 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion.

After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously twice daily for 14 days.

In group 2, atezolizumab will be administered every 4 weeks.

Patients will be monitored closely throughout the study. The treatment and observation phase ends 3 years post infusion.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Pathologically confirmed advanced and/or metastatic solid tumor

- Patients may enter screening procedure before, during, or after the last available indicated standard of care treatment. There is no limitation for prior anti cancer treatments.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- HLA phenotype positive

- Measurable disease and accessible to biopsy

- Adequate pulmonary function per protocol

- Acceptable organ and bone marrow function per protocol

- Acceptable coagulation status per protocol

- Adequate hepatic function per protocol

- Serum creatinine within normal range for age OR creatinine clearance with a recommended estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2

- Patient's tumor must express tumor antigen by qPCR using a fresh tumor biopsy specimen

- Life expectancy more than 3 months

- Confirmed availability of production capacities for IMA203 product

- 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.

- For hepatocellular carcinoma (HCC) patients only, Child-Pugh score of ≤ 6

- IMA203 product must have passed all of the release tests

- Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203

- Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203

- Hepatocellular carcinoma (HCC) patients with liver cirrhosis only - upper endoscopy is required within 6 months of study entry

- The patient must have recovered from any side effects of prior therapy to Grade 1 or lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo) prior to lymphodepletion. As determined by the investigator, the patient may still be eligible if the patient has not fully recovered from Grade ≥ 2 toxicities if these toxicities are not anticipated to further improve (e.g., chronic neuropathy) and such toxicities are not anticipated to worsen with the lymphodepletion therapy

Exclusion Criteria:

- History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years

- Solid tumors with low likelihood of tumor biomarker expression per protocol

- 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 hypersensitivity to cyclophosphamide (CY), fludarabine (FLU), or IL-2

- History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician

- HIV infection, active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, ongoing active anti-HCV treatment or detectable HBV or HCV viral load at the most recent laboratory report. Patients with both HBV and HCV infections will be excluded from screening

1. Patients with a history of HCV infection and with an undetectable viral load per the most recent laboratory report and/or completed anti-HCV treatment but are HCV antibody positive are permitted.

2. History of treated HBV infection is permitted if the viral load is undetectable per the most recent laboratory report. Note: HCC patients with controlled HBV infection, as defined by resolved (anti-hepatitis B surface antigen [HBs-Ag] antibody (Ab) negative, anti-core antigen [HBc Ag] Ab positive) or chronic stable (anti HBs-Ag Ab positive) HBV infection will be eligible for screening. Patients with active HBV infection who are not on anti-HBV treatment will be excluded.

- Any condition contraindicating leukapheresis

- Patients with active brain metastases

NOTE: Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude the existence of currently active brain metastasis, and steroid therapy has been discontinued for ≥2 weeks.

• Treatment with protocol-defined excluded treatments, medical devices, and/or procedures per protocol

For atezolizumab treatment, patients must have adequate hematologic recovery, must have recovered from infections to Grade 1 or lower, and 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.).

Studien-Rationale

Primary outcome:

1. Incidence of adverse events (AE) (Time Frame - up to 3 years post treatment)



Secondary outcome:

1. Persistence of T-cells (Time Frame - up to 3 years post treatment)

2. Tumor response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST) (Time Frame - up to 12 months)

Studien-Arme

  • Experimental: IMA203 Product
    Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA203 product will be infused intravenously. Three dose levels will be evaluated. At least three patients per cohort will be treated. Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2
  • Experimental: IMA203 Product + atezolizumab
    Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA203 product will be infused intravenously. Two dose levels will be evaluated. At least three patients per cohort will be treated. Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2 Treatment with atezolizumab: starting 2 lower doses every 2 weeks, followed by every 4 weeks for 1 year

Geprüfte Regime

  • IMA203 Product:
    Three dose levels (DL) of IMA203 product will be evaluated. The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • IMADetect:
    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.
  • Atezolizumab (Tecentriq):
    Atezolizumab group will be initiated after clearing the single arm for safety. Atezolizumab will be given post IMA203 infusion, after hematologic recovery is achieved, every 4 weeks for up to a year after IMA203 infusion.

Quelle: ClinicalTrials.gov


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