ACTolog in Patients With Solid Cancers

NCT ID: NCT02876510

Last Updated: 2025-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-30

Study Completion Date

2021-09-22

Brief Summary

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The study purpose is to learn about the safety and tolerability of IMA101 alone (Cohort 1) or in combination with atezolizumab (Cohort 2) in patients with advanced solid cancers that express pre-defined Immatics tumor targets.

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Detailed Description

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SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) and the main biomarkers screening. If the patient is eligible, white blood cells will be collected with a leukapheresis for the manufacture of the IMA101 product.

MANUFACTURE: IMA101 product will be made from the patient's white blood cells.

TREATMENT: IMA101 product will be administered to the patient intravenously after lymphodepleting pre-conditioning with chemotherapy (fludarabine and cyclophosphamide).

Low-dose IL-2 will be self-administered twice daily for a total of 28 doses after infusion of IMA101 product. In Cohort 2, atezolizumab will be administered every 3 weeks, starting no earlier than 3 weeks after the IMA101 product infusion and after hematologic recovery.

Patients will be monitored closely throughout the study.

Conditions

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Cancer Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IMA101 product only (Cohort 1)

* Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide
* Infusion of the IMA101 T-cell product(s)
* Post-infusion administration of low-dose recombinant human interleukin-2

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

Fludarabine infusion

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide infusion

IMA101 product

Intervention Type BIOLOGICAL

i.v. infusion of IMA101 product(s).

Recombinant human interleukin-2

Intervention Type BIOLOGICAL

Low dose IL-2 Infusion for two weeks

IMADetect

Intervention Type DIAGNOSTIC_TEST

IMADetect is a laboratory test that is part of screening used to determine the mRNA expression of ACTolog target source genes in tumor biopsies from solid tumors. IMADetect is intended for investigational use only.

IMA101 product + atezolizumab (Cohort 2)

* Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide
* Infusion of the IMA101 T-cell product(s)
* Post-infusion administration of low-dose recombinant human interleukin-2
* Treatment with atezolizumab every 3 weeks after IMA101 product infusion, for 1 year

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

Fludarabine infusion

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide infusion

IMA101 product

Intervention Type BIOLOGICAL

i.v. infusion of IMA101 product(s).

Recombinant human interleukin-2

Intervention Type BIOLOGICAL

Low dose IL-2 Infusion for two weeks

IMADetect

Intervention Type DIAGNOSTIC_TEST

IMADetect is a laboratory test that is part of screening used to determine the mRNA expression of ACTolog target source genes in tumor biopsies from solid tumors. IMADetect is intended for investigational use only.

Atezolizumab

Intervention Type DRUG

Atezolizumab infusion will be given no earlier than 3 weeks post IMA101 infusion and after hematologic recovery is achieved, thereafter every 3 weeks until 1 year after IMA101 infusion.

Interventions

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Fludarabine

Fludarabine infusion

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide infusion

Intervention Type DRUG

IMA101 product

i.v. infusion of IMA101 product(s).

Intervention Type BIOLOGICAL

Recombinant human interleukin-2

Low dose IL-2 Infusion for two weeks

Intervention Type BIOLOGICAL

IMADetect

IMADetect is a laboratory test that is part of screening used to determine the mRNA expression of ACTolog target source genes in tumor biopsies from solid tumors. IMADetect is intended for investigational use only.

Intervention Type DIAGNOSTIC_TEST

Atezolizumab

Atezolizumab infusion will be given no earlier than 3 weeks post IMA101 infusion and after hematologic recovery is achieved, thereafter every 3 weeks until 1 year after IMA101 infusion.

Intervention Type DRUG

Other Intervention Names

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Fludarabine monophosphate Cytoxan Aldesleukin Proleukin Tecentriq

Eligibility Criteria

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Inclusion Criteria

1. Patients must have pathologically confirmed advanced/metastatic cancer prior to enrollment.
2. HLA phenotype positive.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Life expectancy \> 6 months prior to enrollment.
5. Patient is a candidate for a maximum of one further line of established therapy (prior to treatment with ACTolog).
6. The patient has adequate organ and marrow function per protocol
7. At least one lesion (metastasis or primary tumor) being considered accessible by non-high-risk collection procedures for biopsy.
8. The patient has adequate hepatic function per protocol
9. The patient has serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.
10. The patient has adequate pulmonary function per protocol
11. Acceptable coagulation status
12. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
13. Male subjects must agree to use effective contraception or abstinence while on study and for 90 days after infusion of the ACTolog T-cell product.
14. Ability of subject to understand and the willingness to sign written informed consent for study participation.
15. Confirmed availability of production capacities for the patient's ACTolog products.
16. ACTolog target expression as evaluated by the in vitro diagnostic device IMA\_Detect: Patient's tumor must express at least one ACTolog target as assessed by quantitative PCR (qPCR) (to be assessed from a tumor biopsy to be performed if all other eligibility criteria are met).

Exclusion Criteria

1. Any condition contraindicating leukapheresis.
2. Patients with brain metastases. 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.
3. HIV infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue. If positive test results are not indicative of an active infection, patients can be included.
4. Treatment with excluded therapy per protocol
5. Previous extensive radiotherapy to the lung or liver during the last 4 months prior to lymphodepletion regimen.
6. The patient has cardiac conditions defined per protocol
7. Patients with prior stem cell transplantation or solid organ transplantation.
8. The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
9. Active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
10. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years.
11. The patient is pregnant or is breastfeeding.
12. Serious autoimmune disease per protocol
13. History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.
14. Immunosuppression, not related to prior treatment for malignancy.
15. History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.
16. Patients with Grade 3 or higher immune-related toxicities related to prior checkpoint inhibitors
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role collaborator

Immatics US, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cedrik Britten, M.D.

Role: STUDY_DIRECTOR

Immatics US, Inc.

Locations

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University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Tsimberidou AM, Guenther K, Andersson BS, Mendrzyk R, Alpert A, Wagner C, Nowak A, Aslan K, Satelli A, Richter F, Kuttruff-Coqui S, Schoor O, Fritsche J, Coughlin Z, Mohamed AS, Sieger K, Norris B, Ort R, Beck J, Vo HH, Hoffgaard F, Ruh M, Backert L, Wistuba II, Fuhrmann D, Ibrahim NK, Morris VK, Kee BK, Halperin DM, Nogueras-Gonzalez GM, Kebriaei P, Shpall EJ, Vining D, Hwu P, Singh H, Reinhardt C, Britten CM, Hilf N, Weinschenk T, Maurer D, Walter S. Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer. Cancer Immunol Res. 2023 Jul 5;11(7):925-945. doi: 10.1158/2326-6066.CIR-22-0444.

Reference Type DERIVED
PMID: 37172100 (View on PubMed)

Fritsche J, Rakitsch B, Hoffgaard F, Romer M, Schuster H, Kowalewski DJ, Priemer M, Stos-Zweifel V, Horzer H, Satelli A, Sonntag A, Goldfinger V, Song C, Mahr A, Ott M, Schoor O, Weinschenk T. Translating Immunopeptidomics to Immunotherapy-Decision-Making for Patient and Personalized Target Selection. Proteomics. 2018 Jun;18(12):e1700284. doi: 10.1002/pmic.201700284. Epub 2018 Apr 10.

Reference Type DERIVED
PMID: 29505699 (View on PubMed)

Other Identifiers

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IMA101-101

Identifier Type: -

Identifier Source: org_study_id

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