ACTolog in Patients With Solid Cancers (ACTolog)

Study Description

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Brief Summary:

In the IMA101-101 study, patients with relapsed and/or refractory solid cancers will be treated with autologous CD8+ T-cell products (IMA101) specific for novel targets from the ACTolog warehouse that have been identified by the XPRESIDENT target discovery platform.

ACTolog is an actively personalized immunotherapy approach in cancer treatment. The ACTolog clinical trial IMA101-101 is a first-in-human trial for the ACTolog concept for patients with advanced stage solid cancers.

The goal of this clinical research study is to learn about the safety of giving IMA101 to patients with advanced cancer. IMA101 is made with T cells (a type of immune cell) that are grown in the laboratory. Researchers also want to learn if IMA101 can help to control the disease.

Condition or disease	Intervention/treatment	Phase
Cancer; Solid Tumor	Drug: Fludarabine; Drug: Cyclophosphamide; Biological: IMA101 T-cell product; Biological: Recombinant human interleukin-2; Diagnostic Test: IMA_Detect	Phase 1

Detailed Description:

First, patients will enter the screening process.

Screening part 1: Patients may enter the screening procedure when presenting with recurrent/progressing and/or refractory solid cancers when one line of established therapy remains. ACTolog treatment will be applied, if no established treatment is available or treatment is no longer warranted or refused by the patient. During the screening procedures, an HLA test and other medical exams will be done. Only HLA-A*02:01 positive patients can benefit from ACTolog's IMA101 treatment.

Screening part 2: If the patient is HLA-A*02:01 positive and all other initial eligibility criteria are met, a tumor biopsy will then be performed and tested by an investigational diagnostic assay called IMA_Detect. The collected tumor material will be tested for the expression of biomarker targets. At least one of the biomarkers must be positive because expression of these biomarkers indicates the presence of the target structures on the tumor cells against which the study drug will be directed.

If the tumor has none of the specific biomarkers tested by IMA_Detect, the patient will not be eligible for the treatment portion of the study. No further study tests will be done. Only if the patient's tumor has one or more specific biomarkers, and is deemed eligible, may the patient enter the manufacturing phase.

Patients who were biomarker negative in other Immatics' trials, but tested positive for at least one ACTolog biomarker by IMA_Detect may enter screening in order to avoid a new tumor biopsy and repeated biomarker testing.

Manufacturing Phase: During production of the patient's T-cell product, the patient will receive anti-cancer therapy. The leukapheresis product will be made into one to four ACTolog products and frozen until infusion.

Treatment Phase: If the last established therapy option is no longer warranted or refused by the patient, IMA101 T-cell product will be administered to the patient intravenously after a lymphodepleting pre-conditioning with chemotherapy (fludarabine and cyclophosphamide).

Low-dose IL-2 will be self-administered after IMA101 T-cells for 14 days.

Patients will be monitored closely throughout the study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	31 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I Adoptive Cellular Therapy Trial With Endogenous CD8+ T-cells (ACTolog; IMA101) in Patients With Relapsed and/or Refractory Solid Cancers
Actual Study Start Date :	June 30, 2017
Estimated Primary Completion Date :	February 28, 2019
Estimated Study Completion Date :	August 31, 2019

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Treatment; 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

Drug: Fludarabine; Fludarabine infusion; Other Name: Fludarabine monophosphate; Drug: Cyclophosphamide; Cyclophosphamide infusion; Other Name: Cytoxan; Biological: IMA101 T-cell product; i.v. infusion of IMA101 product(s).; Biological: Recombinant human interleukin-2; Low dose IL-2 Infusion for two weeks; Other Names: Aldesleukin; Proleukin; Diagnostic Test: IMA_Detect; IMA_Detect 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. IMA_Detect is intended for investigational use only.

Outcome Measures

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Primary Outcome Measures :

1. Incidence of adverse events (Safety and tolerability) [ Time Frame: Until end of trial, appr. 2 years ]

Secondary Outcome Measures :

1. Incidence of successfully manufactured personalized T-cell products per patient (Feasibility of the ACTolog process) [ Time Frame: Until end of trial, appr. 2 years ]
2. Peripheral T-cell persistence (assessment of frequency of T-cells over time) [ Time Frame: Until end of trial, appr. 2 years ]
3. T-cell functionality as assessed by cellular immunomonitoring [ Time Frame: Until end of trial, appr. 2 years ]
4. Incidence of clinical responders [ Time Frame: Until end of trial, appr. 2 years ]
5. Description of overall survival (OS) [ Time Frame: Until end of trial, appr. 2 years ]
6. Description of progression-free survival (PFS) [ Time Frame: Until end of trial, appr. 2 years ]
7. Determine and report the success rate of completely evaluable results of IMA_Detect from all biopsies collected [ Time Frame: Until end of trial, appr. 2 years ]

Other Outcome Measures:

1. Biobanking for tumor and RNA samples for future IMA_Detect validation studies [ Time Frame: Until the end of the trial, appr. 2 years ]
2. Biomarker assessment (Descriptive reporting of cellular, serum and tumor biomarker as well as clinical parameters) • Description of effector functions of antigen specific T cells within PBMCs [ Time Frame: Until end of trial, appr. 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Pathologically confirmed advanced/metastatic cancer
2. HLA phenotype HLA-A*02:01
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. Life expectancy > 6 months
5. Patient is a candidate for a maximum of 1 line of established therapy (prior to treatment with ACTolog).
6. Normal organ and marrow function
7. At least 1 lesion considered accessible for a by non-high risk collection procedures for biopsy.
8. Adequate hepatic function defined per protocol.
9. Serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.
10. Adequate pulmonary function and oxygen saturation.
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 qPCR (to be assessed from a tumor biopsy to be performed if all other eligibility criteria are met).

NOTE: Patients who were biomarker negative in other Immatics' trials, but tested positive for at least one ACTolog biomarker may enter screening.

TREATMENT INCLUSION CRITERIA:

- Patients may enter the treatment phase if disease recurs/progresses, becomes refractory or after termination of last-line therapy OR if continuation of last line therapy is no longer warranted OR if the patient refuses to continue established treatments AND if the following eligibility criteria are met:

• At least one ACTolog product was successfully produced for the patient.
• Signed informed consent form.
• ECOG performance status 0-2.
• Adequate hepatic function (defined above)
• Serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.
• Evaluable disease

Exclusion Criteria:

1. Any condition contraindicating leukapheresis.
2. Patients with brain metastases.
3. HIV infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics
4. Previous extensive radiotherapy to the lung or liver during the last 4 months prior to lymphodepletion regimen.
5. The patient has cardiac conditions per protocol
6. Prior stem cell transplantation or solid organ transplantation.
7. Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
8. Active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
9. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 5 years.
10. Pregnant or is breastfeeding.
11. Serious autoimmune disease at the discretion of the treating attending
12. History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.
13. Immunosuppression, not related to prior treatment for malignancy.
14. History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.

TREATMENT EXCLUSION CRITERIA

• Received chemotherapy, surgery, radiotherapy (for therapeutic purposes), tyrosine kinase inhibitor (TKI) (e.g. erlotinib, gefitinib), investigational drugs, chronic use of systemic corticosteroids or statin therapy within 2 weeks prior to lymphodepletion regimen.
• Previous extensive radiotherapy to the lung or liver during the last 4 months prior to lymphodepletion regimen.

Contacts and Locations

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Contacts

Contact: Hong Ma, M.D.	346-204-5400	ma@immatics.com

Locations

United States, Texas
University of Texas MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Apostolia M. Tsimberidou, M.D., Ph.D.

Sponsors and Collaborators

Immatics US, Inc.

M.D. Anderson Cancer Center

Investigators

Study Director:	Hong Ma, M.D.	Immatics US, Inc.

More Information

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Additional Information:

Immatics website 

University of Texas MD Anderson Cancer Center website 

Responsible Party:	Immatics US, Inc.
ClinicalTrials.gov Identifier:	NCT02876510 History of Changes
Other Study ID Numbers:	IMA101-101
First Posted:	August 23, 2016
Last Update Posted:	February 8, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		Yes
Device Product Not Approved or Cleared by U.S. FDA:		Yes
Pediatric Postmarket Surveillance of a Device Product:		No

Keywords provided by Immatics US, Inc.:

Ovarian Cancer; Esophageal Cancer; Head and neck squamous cell carcinoma; Squamous non-small cell lung cancer; Gastric Cancer

Additional relevant MeSH terms:

Cyclophosphamide; Fludarabine phosphate; Fludarabine; Aldesleukin; Interleukin-2; Vidarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action	Antineoplastic Agents; Myeloablative Agonists; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-HIV Agents; Anti-Retroviral Agents