Clinical trial NCT03686124: ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Refractory Cancer
Recurrent Cancer
Solid Tumor, Adult
Cancer
Keywords: T-cell therapy
immunotherapy
Melanoma (Skin)
Melanoma, Uveal
Ovarian Carcinoma
Uterine Carcinoma
Uterine Carcinosarcoma
Immatics
Lead sponsor: Immatics US, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-26
Enrollment: 476
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 or 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, if applicable, a low dose of IL-2 will be given subcutaneously until day 10.

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.

Eligibility criteria: 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-A\*02:01 positive
* 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 5 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 2.0-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

Primary outcomes:
measure: Evaluate safety and tolerability of treatment with treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab
timeFrame: 35 days
measure: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8
timeFrame: 28 days
Secondary outcomes:
measure: Persistence of T-cells
timeFrame: up to 5 years post treatment
measure: Tumor response
timeFrame: up to 5 years
measure: Tumor response
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Boston
country: United States
facility: Massachussettes General Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)
state: Baden-Württemberg
city: Munich
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
state: Bavaria
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
state: Bavaria
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn - Medizinische Klinik III
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
state: Rhineland-Palatinate
city: Dresden
country: Germany
facility: Universitätsklinikum C.-G.-Carus Dresden
state: Saxony
city: Berlin
country: Germany
facility: Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
Study officials:
affiliation: Immatics US, Inc.
name: Cedrik Britten, M.D.
role: STUDY_DIRECTOR
References: