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Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer

NCT02933944

Description:

The purpose of this study is to determine safety and anti-tumor immune activation generated by TG02 and Granulocyte macrophage colony stimulating factor (GM-CSF), first as monotherapy (Part I), thereafter in combination with the checkpoint inhibitor pembrolizumab (Part II), in patients with locally advanced primary and recurrent colorectal cancer scheduled to have surgery. Part I will include 4-6 patients and Part II will include up to 10 patients. Part I and Part II are separate and independent sequential components of the study. Patients will only be able to participate in either the Part I cohort or Part II cohort. Main objective of the study is to investigate safety and immune response after TG02-treatment.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
  • Official Title: A Non-Randomised Open-Label Phase Ib Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: CT TG02-01
  • NCT ID: NCT02933944

Conditions

  • Rectal Cancer

Interventions

DrugSynonymsArms
TG02-treatmentTG02-treatment
PembrolizumabTG02-treatment

Purpose

The purpose of this study is to determine safety and anti-tumor immune activation generated by TG02 and Granulocyte macrophage colony stimulating factor (GM-CSF), first as monotherapy (Part I), thereafter in combination with the checkpoint inhibitor pembrolizumab (Part II), in patients with locally advanced primary and recurrent colorectal cancer scheduled to have surgery. Part I and Part II will include approximately 10 patients each. Part I and Part II are separate and independent sequential components of the study. Patients will only be able to participate in either the Part I cohort or Part II cohort. Main objective of the study is to investigate safety and immune response after TG02-treatment.

Trial Arms

NameTypeDescriptionInterventions
TG02-treatmentExperimentalPart I: The TG02-treatment consists of an intradermal injection of GM-CSF followed by an injection of TG02. The GM-CSF is to be given 15-30 minutes before TG02. TG02-treatment will be administered on Days 1, 8, 15, 22 and 36. If surgery after week 10, TG02-treatment will also be given at week 10 (Day 64). Part II: TG02-treatment will be given as described under Part I. In addition pembrolizumab will be administered.
  • TG02-treatment
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with locally advanced primary and recurrent colorectal cancer (CRC)
             (histologically or cytologically confirmed adenocarcinoma), with a confirmed oncogenic
             KRAS exon 2, codon 12 or 13 mutations, eligible for radical pelvic surgery at time of
             enrolment.

          -  Patient is ≥18 years of age and able to consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

          -  Patient has adequate organ and bone marrow function within 28 days of study

               -  Neutrophil count >1.5 x10^9/L

               -  Platelets >100 x10^9/L

               -  Hb >90g/L

               -  Total bilirubin <1.5 upper limit of normal, ULN

               -  ALT and AST <3.0 x ULN

               -  Serum creatinine <3 x ULN or Creatinine Clearance ≥ 30ml/min (Cockroft-Gault or
                  Nuclear GFR method)

               -  PT and APTT <1.3 x ULN

          -  The patient is willing to provide study specific pre TG02-treatment biopsy of tumour
             mass and allow use of archival tumour biopsies. For patients where there are technical
             reasons a baseline biopsy cannot be performed but who fulfil all the other inclusion
             criteria, the investigator shall contact the medical monitor to discuss the
             possibility of including such patient.

          -  The patient is willing and able to comply with the protocol, and agrees to return to
             the hospital for study visits and examinations

          -  Men and women of childbearing potential must use adequate contraception to prevent
             pregnancy during the study. Adequate contraception is defined in the study as any
             medically recommended method (or combination of methods) as per standard of care. An
             adequate contraception includes hormonal contraception with implants or combined oral,
             transdermal or injectable contraceptives, certain intrauterine devices, bilateral
             tubal ligation, hysterectomy, or vasectomy of partner. A combination of male condom
             with either cap, diaphragm or sponge with spermicide are also considered acceptable.
             For women of childbearing potential a negative pregnancy test needs to be confirmed
             before inclusion.

          -  The patient has been fully informed about the study and is willing to participate in
             the study, and has provided written informed consent form prior to any trial specific
             screening procedures.

        Exclusion Criteria:

          -  The patient has previously received an anticancer vaccine or immune checkpoint
             inhibitor, or participated in a trial involving the use of an anticancer vaccine or
             immune checkpoint inhibitor

          -  Patients where pre-surgery radiotherapy, chemotherapy or other anti-cancer therapy has
             not been completed ≥ 2 weeks prior to TG02-treatment

          -  The patient has had a prior different malignancy within the last 3 years (excluding
             adequately treated basal cell or squamous cell carcinoma of the skin cancer, or
             localised low grade tumours considered cured and not requiring systemic therapy)

          -  The patient has uncontrolled or significant intercurrent or recent illness including:

               -  auto-immune disorder or history of autoimmune disease requiring immunosuppressive
                  treatment.

               -  cardiac disorder such as uncontrolled cardiac failure, unstable angina or non-ST
                  segment elevation myocardial infarction (NSTEMI) or myocardial infarction,
                  uncontrolled arrhythmia less than 3 months before screening

               -  stroke or thromboembolic event within 3 months of study commencement

               -  active or uncontrolled severe infection

               -  history of solid organ transplantation or any condition requiring chronic
                  treatment with corticosteroids or other immunosuppressive agents

               -  active coagulopathy/bleeding diathesis

               -  cirrhosis, chronic active or untreated persistent hepatitis

               -  history of adverse reactions to peptide vaccines

          -  The patient is pregnant or lactating.

          -  Has received an investigational drug within 4 weeks prior to study drug
             administration, or unless other has been agreed with the medical monitor

          -  Is currently receiving any agent with a known effect on the immune system, unless at
             dose levels that are not immunosuppressive (e.g. prednisone at 10 mg/day or less or as
             inhaled steroid at doses used for the treatment of asthma)

          -  Known history of positive tests for HIV/AIDS

          -  Are planned to receive yellow fever or other live (attenuated) vaccines during the
             course of study

          -  For Part II - any contraindication to receiving pembrolizumab:

        Hypersensitivity to the active substance (pembrolizumab) or to any of the excipients;
        L-histidine, L-histidine hydrochloride monohydrate, Sucrose, Polysorbate 80
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events
Time Frame:From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Change of immune suppression factors e.g. PD-1 and T-reg from pre to post treatment
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Change in pathological responses and markers of apoptosis in tumour tissue
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Changes in standard uptake values (SUV) will be assessed by FDG PET-CT images
Time Frame:From screening until surgery
Safety Issue:
Description:
Measure:Changes in the tumour marker Carcinoembryonic Antigen (CEA) throughout treatment will be assessed by analysis of blood samples to follow the evolution of disease under treatment
Time Frame:From screening until surgery
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Targovax ASA

Trial Keywords

  • locally recurrent

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