MYPHISMO: MYB and PD-1 Immunotherapies Against Multiple Oncologies Trial

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Brief Title

MYPHISMO: MYB and PD-1 Immunotherapies Against Multiple Oncologies Trial

Official Title

First-in-human Phase I Clinical Trial of a Combined Immune Modulatory Approach Using TetMYB Vaccine and Anti-PD1 Antibody in Patients With Advanced Solid Cancer Including Colorectal or Adenoid Cystic Carcinoma.

Brief Summary

      The purpose of this research study is to look at the effects, good or bad, of TetMYB Vaccine
      in combination with BGB-A317 in patients with advanced or metastatic solid cancers (including
      colorectal or adenoid cystic cancer).

      The immune system is the body's defence against cancer, bacteria and viruses. TetMYB Vaccine
      is a vaccine that helps your immune system to recognise the cancer cells. BGB-A317 is an
      antibody (a type of protein made in the body in response to a foreign substance) that helps
      to stop or reverse the growth of tumour cells.

      Up to 32 participants may take part in this study, which is divided into 2 stages: dose
      escalation (different doses will be tested in small groups of patients) and dose expansion
      (one or more doses may be tested in a larger group of patients). Which stage you participate
      in will depend on which is open at the time. Your study doctor will discuss this with you.

      During dose escalation, study patients will receive increasing doses of the TetMYB Vaccine,
      starting at a low dose. During dose expansion, study patients will receive the dose
      determined as safe in dose escalation.

      The study design is as follows:

      In the dose finding stage, the first patient of each dose level will receive 6 consecutive
      weekly doses of intradermal TetMYB monotherapy for safety evaluation. If there are no
      reported DLTs, the next 2 patients of the same dose level will also receive 6 consecutive
      weekly intradermal doses of TetMYB, however with 3 weekly doses of BGB-A317 commencing with
      the fourth TetMYB dose. The dosage of TetMYB are as follows:

        -  Dose level 1: 100 ug in 100 uL of sterile dH2O containing 5% DMSO

        -  Dose level 2: 500 ug in 100 uL of sterile dH2O containing 5% DMSO

        -  Dose level 3: 1000 ug in 100 uL of sterile dH2O containing 5% DMSO.

      In the dose expansion stage, the dosage will be the maximum tolerated dose (MTD) identified
      in the dose-finding stage and in combination with BGB-A317.

      TetMYB Vaccine is being developed and manufactured by the Peter MacCallum Cancer Centre
      according to Good Manufacturing Practice (GMP) and in accordance with guidelines provided by
      the Food and Drug Administration (FDA) in the USA and Therapeutic Goods Administration (TGA)
      in Australia. TetMYB Vaccine is an experimental treatment and is currently not approved for
      use in any country. This means that it is not an approved treatment for cancer in Australia.
      This will be the first time that the TetMYB vaccine is given to humans.

      BGB-A317 is being developed by BeiGene, a biopharmaceutical company. BGB-A317 is an
      experimental treatment. This means that it is not an approved treatment for solid cancers in
      Australia.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

The incidence of Grade 3 or 4 or greater adverse events (AEs) according to CTCAE v4.03 criteria and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs).

Secondary Outcome

 Tolerability of the treatment as defined as receiving a minimum of 4 doses of TetMYB Vaccine within 6 weeks of starting treatment.

Condition

Colorectal Cancer

Intervention

TetMYB Vaccine

Study Arms / Comparison Groups

 TetMYB Vaccine & BGB-A317
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

32

Start Date

May 30, 2018

Completion Date

December 30, 2022

Primary Completion Date

December 30, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female aged 18 years or older at screening.

          2. Patients with advanced/metastatic colorectal or adenoid cystic carcinoma; for which no
             effective standard therapy is available.

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

          4. Measurable disease as per irRECIST criteria 1.1.

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

          6. Life expectancy greater than 3 months.

          7. Adequate haematological, renal and hepatic functions as defined by:

               -  Neutrophil count >1.5 x 109/L

               -  Platelets >100 x 109/L

               -  Hb >100 g/L (Patients can be transfused in the lead-in period, providing they do
                  not have active bleeding or require regular transfusions)

               -  Total bilirubin <1.5x upper limit of normal (ULN)

               -  ALT and AST <2.5x ULN (<5.0x ULN for patients with hepatic metastasis)

               -  Serum creatinine <1.5x ULN or Creatinine Clearance >50 mL/min (Cockcroft-Gault or
                  Nuclear GFR method)

          8. Willing to provide study specific pre-treatment biopsy of tumour and allow use of
             archival tumour biopsies. This is optional for adenoid cystic carcinoma patients.

          9. Willing to consent to the use of their collected fresh tumour and archival FFPE
             specimen and blood samples as detailed in the protocol for research including but not
             limited to DNA, RNA and protein based biomarker detection.

         10. 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. Combinations of male condom
             with either cap, diaphragm or sponge with spermicide are also considered acceptable.
             For women of childbearing age, a negative pregnancy test needs to be confirmed before
             inclusion.

        Exclusion Criteria:

          1. Prior therapy with an anti-cancer vaccine; or anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting
             T-cell co-stimulation or immune checkpoint pathways.

          2. Chemotherapy, radioactive, biological cancer therapy, or tyrosine kinase inhibitor
             (TKI) therapy, within four weeks prior to the first dose of study drug. All toxicities
             attributed to prior anti-cancer therapy other than alopecia and fatigue must have
             resolved to Grade 1 (NCI CTCAE v4.03) or baseline before administration of study drug.

          3. Patient has had a prior malignancy active within the previous 3 years except for
             locally curable cancers that have been apparently cured, such as basal or squamous
             cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or
             breast, or localized prostate cancer.

          4. Uncontrolled or significant intercurrent or recent illness including:

               -  Autoimmune 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

               -  Active or uncontrolled severe infection

          5. History of solid organ transplantation or any condition requiring chronic treatment
             with corticosteroids or other immunosuppressive agents.

          6. Active coagulopathy/bleeding diathesis.

          7. Cirrhosis, chronic active or untreated persistent hepatitis.

          8. Active Hepatitis B: (defined as having a positive Hepatitis B surface antigen [HBsAg]
             test at screening). Patients with past or resolved Hepatitis B infection (defined as
             having a negative HBsAg test and a positive IgG antibody to Hepatitis B core antigen
             [anti-HBc]) are eligible. Hepatitis B virus (HBV) DNA must be obtained in these
             patients prior to Cycle 1, Day 1, and must demonstrate no active infection.

          9. Active Hepatitis C: Patients positive for Hepatitis C virus (HCV) antibody are
             eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

         10. History of adverse reactions to peptide vaccines.

         11. Patients who are pregnant or lactating.

         12. Has received an investigational drug within 4 weeks prior to first dose of study drug,
             or unless other has been agreed with the SSC.

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

         14. Known history of positive tests for HIV/AIDS.

         15. Prior treated brain metastases must be without evidence of progression (through
             magnetic resonance imaging [MRI] with contrast - preferred method or contrast enhanced
             computed tomography [CT]) for at least 4 weeks and off immunosuppressive doses of
             systemic medications, such as steroids (doses > 10 mg/day prednisone or equivalent)
             for at least 2 weeks before study drug administration to be eligible

         16. Receipt of live, attenuated vaccine within 28 days prior to the first dose of study
             drug (Note: Subjects, if enrolled, should not receive live vaccine during the study
             and 180 days after the last dose of study drug).

         17. Any contraindication to receiving anti-PD-1 antibody (BGB-A317) or hypersensitivity to
             the constituents of BGB-A317.

         18. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator.

         19. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jayesh Desai, +61 8559 7810, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT03287427

Organization ID

MYPHISMO


Responsible Party

Sponsor

Study Sponsor

Peter MacCallum Cancer Centre, Australia


Study Sponsor

Jayesh Desai, Principal Investigator, Peter MacCallum Cancer Centre, Australia


Verification Date

March 2018