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

Cancer Clinical Trial

— ACTengine  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03686124
• Other study ID #: IMA203-101
• Status: Recruiting
• Phase: Phase 1
• Start date: May 14, 2019
• Est. completion date: December 2028

Study information

• Verified date: October 2023
• Source: Immatics US, Inc.
• Contact: Immatics US, Inc.
• Phone: +1 346 204-5400
• Email: ctgovinquiries[@]immatics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Recurrence
• Recurrent Cancer
• Refractory Cancer
• Solid Tumor, Adult

Intervention

Biological:
• IMA203 Product
The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
• IMA203CD8 Product
The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.

Device:
• 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.

Drug:
• nivolumab (Opdivo®)
Nivolumab will be given post IMA203 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.

Locations

Country	Name	City	State
Germany	Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie	Berlin
Germany	Universitätsklinikum Bonn - Medizinische Klinik III	Bonn	North Rhine-Westphalia
Germany	Universitätsklinikum C.-G.-Carus Dresden	Dresden	Saxony
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Würzburg	Würzburg	Bavaria
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Immatics US, Inc.

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8	Number of patients with dose-limiting toxicities (DLTs)	28 days
Secondary	Persistence of T-cells	Measurement of TCR-engineered T cells in peripheral blood	up to 5 years post treatment
Secondary	Tumor response	Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	up to 12 months
Secondary	Tumor response	Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)	up to 12 months