Clinical Trials /

ACTolog in Patients With Solid Cancers

NCT02876510

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ACTolog in Patients With Solid Cancers
  • Official Title: Phase I Adoptive Cellular Therapy Trial With Endogenous CD8+ T Cells (ACTolog® IMA101) Alone or in Combination With Atezolizumab in Patients With Relapsed and/or Refractory Solid Cancers

Clinical Trial IDs

  • ORG STUDY ID: IMA101-101
  • NCT ID: NCT02876510

Conditions

  • Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
FludarabineFludarabine monophosphateIMA101 product only (Cohort 1)
CyclophosphamideCytoxanIMA101 product only (Cohort 1)
IMA101 productIMA101 product only (Cohort 1)
Recombinant human interleukin-2Aldesleukin, ProleukinIMA101 product only (Cohort 1)
AtezolizumabTecentriqIMA101 product + atezolizumab (Cohort 2)

Purpose

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.

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
IMA101 product only (Cohort 1)ExperimentalPre-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
  • Fludarabine
  • Cyclophosphamide
  • IMA101 product
  • Recombinant human interleukin-2
IMA101 product + atezolizumab (Cohort 2)ExperimentalPre-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 6 months
  • Fludarabine
  • Cyclophosphamide
  • IMA101 product
  • Recombinant human interleukin-2
  • Atezolizumab

Eligibility 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. 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. 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.

         16. Patients with Grade 3 or higher immune-related toxicities related to prior checkpoint
             inhibitors
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (Safety and tolerability)
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of successfully manufactured personalized T-cell products per patient (Feasibility of the ACTolog process)
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure:Peripheral T-cell persistence (assessment of frequency of T-cells over time)
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure:T-cell functionality as assessed by cellular immunomonitoring
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure:Incidence of clinical responders
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure:Description of overall survival (OS)
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure:Description of progression-free survival (PFS)
Time Frame:Until end of trial, appr. 2 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immatics US, Inc.

Trial Keywords

  • 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
  • IMA101
  • atezolizumab
  • Tecentriq

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