ACTolog in Patients With Solid Cancers (ACTolog)

Study Description

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Brief Summary:

The study purpose is to learn about the safety and tolerability of IMA101 in patients with advanced solid cancers.

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

Detailed Description:

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 taken during 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 a lymphodepleting pre-conditioning with chemotherapy (fludarabine and cyclophosphamide).

Low-dose IL-2 will be self-administered twice daily after IMA101 product for a period of time.

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 :	June 2019
Estimated Study Completion Date :	September 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 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. 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 and oxygen saturation >92% on room air.
11. Acceptable coagulation status: INR ≤2.0 x ULN and PTT ≤2.0 x ULN.
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.
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. The patient has 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 leukapheresis.
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: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) or autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic Lupus Erythematosus or autoimmune vasculitis [e.g. Wegener's Granulomatosis] are excluded from this study.
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.

Contacts and Locations

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Contacts

Contact: Rebecca Griffith-Eskew	346-204-5359	griffith-eskew@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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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:	July 11, 2018
Last Verified:	July 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.:

IMA101; Ovarian Cancer; Esophageal Cancer; Head and neck squamous cell carcinoma; non-small cell lung cancer; Gastric Cancer	T-cell Therapy; immunotherapy; adoptive cellular therapy; T-cell receptor; cell therapy; cytotherapy

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