Clinical Trials /

PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO)

NCT03391232

Description:

Phase I/II clinical trial investigates the safety, tolerability, immunogenicity and preliminary efficacy of multiple doses of PolyPEPI1018 CRC vaccine as an add-on treatment to the standard-of-care maintenance therapy in patients with metastatic colorectal cancer. Clinical responses will be evaluated by indiction of T cell responses, T lymphocyte infiltration in accessible biopsy sites, and by objective tumor responses. This study will also explore the accuracy of the predicted T cell responses in each patient using the candidate companion diagnostic test and the correlations between clinical responses and predicted T cell responses.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Immunogenicity of PolyPEPI1018 Vaccine in the Treatment of Metastatic Colorectal Cancer (OBERTO)
  • Official Title: Single Dose, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Subcutaneous Injection of PolyPEPI1018 Vaccine as an Add-on Immunotherapy to the Standard-of-Care Maintenance Therapy in Subjects With Metastatic Colorectal Cancer (CRC)

Clinical Trial IDs

  • ORG STUDY ID: OBERTO 101
  • NCT ID: NCT03391232

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
Cancer ImmunotherapyPolyPEPI1018 CRC Vaccine

Purpose

TREOS' Phase I clinical trial will investigate the safety, tolerability, and immunogenicity of a single dose of PolyPEPI1018 CRC Vaccine as an add-on treatment to the standard-of-care maintenance therapy in patients with metastatic colorectal cancer. This study will also explore the accuracy of prediction of pre-existing and newly induced CD8+ T cell responses in each patient using the PEPI Test and T lymphocyte infiltration detected in accessible biopsy sites.

Detailed Description

      This is a Phase 1, open-label, single-arm, multicenter study to evaluate the safety,
      tolerability, and immunogenicity of a single subcutaneous (SC) injection of PolyPEPI1018 as
      an add-on immunotherapy to the standard-of-care maintenance therapy in approximately 10
      subjects with mCRC.

      The study is composed of a 3‑week Screening Period, the administration of a single dose
      vaccine (Day 1, Week 0), and a 12‑week Follow‑up Period. The study will be conducted on an
      outpatient basis.

      Screening should be performed in parallel with the subject's completion of the
      standard-of-care first-line treatment and initiation of the standard-of-care maintenance
      treatment.

      The single dose of PolyPEPI1018 will be administered after the subject initiates the
      maintenance regimen, and within 3 weeks after the eligibility CT scan was performed (should
      be performed at the completion of the first-line treatment).

      Subjects will be monitored every 3 weeks for 12 weeks after administration of PolyPEPI1018
      (i.e. Weeks 3, 6, 9 and 12).
    

Trial Arms

NameTypeDescriptionInterventions
PolyPEPI1018 CRC VaccineExperimentalThe vaccine contains 6 synthetic peptides mixed with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized with the PEPI biomarker to induce long lasting CRC specific T cell responses.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Male or female subjects, 18-75 years of age at time of Screening who provide written
                 informed consent prior to initiation of any study procedure
    
              2. Histologically confirmed metastatic adenocarcinoma originating from the colon or the
                 rectum
    
              3. Presence of at least 1 measurable reference lesion according to the Response
                 Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
    
              4. Experienced PR or stable disease during first‑line treatment with a systemic
                 chemotherapy regimen and 1 biological therapy regimen
    
              5. Maintenance therapy with 1 biological therapy regimen with or without a systemic
                 chemotherapy regimen scheduled to initiate prior to the first day of treatment with
                 the study drug
    
              6. No more than 1 line of chemotherapy regimen for mCRC (adjuvant therapy for
                 non-metastasized disease is allowed if terminated more than 6 months before Screening
                 and without recurrence within 6 months after the end of adjuvant treatment)
    
              7. Last CT scan at 3 weeks or less before the first day of treatment
    
              8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    
              9. Women of childbearing potential must agree to appropriately use an effective form of
                 contraception (failure rate of <1% per year) for 3 months from the day of the
                 treatment. An effective form of contraception is defined as using hormonal
                 contraceptives or an intrauterine device combined with at least 1 of the following
                 forms of contraception: a diaphragm, cervical cap or condom
    
             10. Men must agree to use an effective form of contraception (as defined above), and not
                 donate sperm for 3 months from the day of the treatment
    
             11. White blood cell count ≥3.0 × 109/L with neutrophils ≥1.5 × 109/L
    
             12. Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL)
    
             13. Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site
    
             14. Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) ≤2.5 × ULN in
                 the absence of liver metastases. ALAT and ASAT ≤5 × ULN set by the site in the
                 presence of liver metastases
    
             15. Serum creatinine ≤1.5 × ULN set by the site and creatinine clearance >30 mL/min using
                 Cockroft formula
    
             16. Relevant toxicities of prior therapies must have resolved, except for
                 oxaliplatin-related neuropathy or alopecia
    
             17. Anticipated life expectancy ≥6 months Subject is willing and able to comply with the
                 requirements of the protocol
    
            Exclusion Criteria:
    
              1. Received chronic systemic immune therapy or immunosuppressant medication other than
                 steroids within the last 6 weeks prior to start of study treatment
    
              2. Received continuous systemic steroid treatment within the last 2 weeks prior to start
                 of study treatment
    
              3. Colorectal cancer with documented high microsatellite instability (MSI‑H)
    
              4. Colorectal cancer with documented BRAF mutations
    
              5. Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency
                 diseases
    
              6. Central nervous system (CNS) metastases
    
              7. Active or uncontrolled severe infections or undiagnosed febrile condition >38ºC
    
              8. Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory
                 diseases
    
              9. Symptomatic peritoneal carcinomatosis
    
             10. Peritonitis
    
             11. Serious, non-healing wounds, ulcers or bone fractures
    
             12. Nephrotic syndrome
    
             13. Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment
                 (except bleeding tumor before tumor resection surgery)
    
             14. Hemorrhagic diathesis or thrombotic tendency
    
             15. Major surgery or radiotherapy within 12 weeks prior to the study treatment or
                 anticipation of needing such procedure during the study period
    
             16. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated
                 drainage more than once every 28 days
    
             17. Participants with active malignancy (other than colorectal cancer) or a prior
                 malignancy within the past 12 months
    
             18. Participant with myocardial infarction within 6 months prior to enrollment or New York
                 Heart Association Class III or IV heart failure, uncontrolled angina, severe
                 uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute
                 ischemia or active conduction system abnormalities. Prior to the first dose of study
                 treatment, any electrocardiogram (ECG) abnormality at Screening must be documented by
                 the investigator as not medically relevant
    
             19. Administration of a live, attenuated vaccine within 4 weeks before randomization or
                 anticipation of a live attenuated vaccine will be required during the study
    
             20. Participant has participated in another clinical study involving an investigational
                 product (IP) or investigational device within 30 days prior to enrollment or is
                 scheduled to participate in another clinical study involving an IP or investigational
                 device during the course of this study
    
             21. Known hypersensitivity to any component of the investigational drug
    
             22. If female, participant is pregnant (exclusion confirmed with beta-human chorionic
                 gonadotropin [hCG] test) or lactating at the time of enrollment, or has plans to
                 become pregnant or start breastfeeding during the study
    
             23. Pre-existing alcohol or drug abuse
    
             24. Medical or mental impairments which make it impossible to obtain the patient's consent
                 or to conduct the study
    
             25. A significant concomitant medical condition which the clinical investigator believes
                 precludes the patient from enrolling in the study Absent or limited legal competence
          
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of Treatment Related Adverse Events
    Time Frame:21 days
    Safety Issue:
    Description:Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment

    Secondary Outcome Measures

    Measure:Prediction of T cell responses
    Time Frame:21 days
    Safety Issue:
    Description:To determine epitopes of PolyPRPI1018 capable of inducing T cell responses in each study subject
    Measure:Measure T cell responses
    Time Frame:12 weeks
    Safety Issue:
    Description:To measure epitope specific T cell responses in each study subjects

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Treos Bio Zrt

    Last Updated

    April 11, 2018