ACTengine: TCR-engineered T Cells in Solid Tumors: IMA202-101

Sponsor

Immatics US, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03441100

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study purpose is to establish the safety and tolerability of IMA202 product in patients with solid tumors that express melanoma-associated antigen 1 (MAGEA1).

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult Refractory Cancer Recurrent Cancer Cancer	Drug: IMA202 Product Device: IMADetect®	Phase 1

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 IMA202 product.

MANUFACTURING: IMA202 product will be made from the patient's white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA202 product infusion to improve the duration of time that IMA202 product stays in the body. The patient will be admitted to the hospital during the treatment.

After the IMA202 product infusion, a low dose of IL-2 will be given twice daily for a period of time.

Patients will be closely monitored for safety and for a total of 3 years post IMA202 infusion.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Recurrent and/or Refractory Solid Tumors(ACTengine® IMA202-101)

Actual Study Start Date :

May 2, 2019

Actual Primary Completion Date :

Jun 17, 2022

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: IMA202 Product Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA202 product will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated. Post-infusion of IMA202 product, administration of low dose recombinant human interleukin-2	Drug: IMA202 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 clinical trials. IMADetect® is intended for investigational use only.

Arm

Intervention/Treatment

Experimental: Experimental: IMA202 Product

Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide One dose of IMA202 product will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated. Post-infusion of IMA202 product, administration of low dose recombinant human interleukin-2

Drug: IMA202 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 clinical trials. IMADetect® is intended for investigational use only.

Outcome Measures

Primary Outcome Measures

Incidence of adverse events (AE) [up to 3 years post treatment]

Secondary Outcome Measures

Persistence of T-cells [up to 3 years post treatment]
Tumor response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST) [up to 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 for the study
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
Adequate renal function per protocol
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 IMA202 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
IMA202 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 IMA202
Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA202
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), IL-2, or any of the rescue medications
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

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.
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, lymphodepletion, low-dose IL-2, and/or IMA202 treatment
Patients with any active viral infection
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
Concurrent participation in an interventional part of another clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
2	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
3	Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11	Regensburg	Bavaria	Germany	93053
4	Universitätsklinikum Würzburg	Würzburg	Bavaria	Germany	97080
5	Universitätsklinikum Bonn - Medizinische Klinik III	Bonn	North Rhine-Westphalia	Germany	53127
6	Universitätsklinikum Münster, Alber-Schweitzer-Campus 1	Münster	North Rhine-Westphalia	Germany	48149
7	Universitätsklinikum C.-G.-Carus Dresden	Dresden	Saxony	Germany	01307
8	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246