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

This is an interventional treatment trial for Colorectal Cancer focused on measuring Advanced, Metastatic Read More

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.