MYPHISMO: MYB and PD-1 Immunotherapies Against Multiple Oncologies Trial (MYPHISMO)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03287427|
Recruitment Status : Not yet recruiting
First Posted : September 19, 2017
Last Update Posted : March 29, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Adenoid Cystic Carcinoma||Drug: TetMYB Vaccine Drug: BGB-A317||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Estimated Study Start Date :||May 30, 2018|
|Estimated Primary Completion Date :||December 30, 2019|
|Estimated Study Completion Date :||December 30, 2022|
|Experimental: TetMYB Vaccine & BGB-A317||
Drug: TetMYB Vaccine
Weekly intra-dermal injections of either 0.1mg, 0.5mg or 1.0mg on day 1 for week 1 to week 6.
3 weekly IV injections of 200mg commencing from Week 4.
- 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). [ Time Frame: End of Week 6 ]
- Tolerability of the treatment as defined as receiving a minimum of 4 doses of TetMYB Vaccine within 6 weeks of starting treatment. [ Time Frame: End of Week 6 ]
- The occurrence, type, severity and relationship to treatment of adverse events occurring after the first 6 weeks of treatment, described according to CTCAE v4.03 criteria. [ Time Frame: Week 7 and through study completion, an average of 12 months. ]
- The objective response as defined by the achievement of a complete (irCR) or partial (irPR) response, based on irRECIST criteria within 12 weeks of first vaccination. [ Time Frame: End of Week 12 ]
- Clinical benefit as defined by wither the achievement of a complete (irCR) or partial (irPR) response as per irRECIST criteria; or the maintenance of stable disease (irSD), as per irRECIST criteria, at 12 weeks after commencement of treatment. [ Time Frame: End of Week 12. ]
- Progression free survival (PFS) as defined as the time from first vaccination to the earliest of date of disease progression as assessed by irRECIST or death from any cause. [ Time Frame: From the date of treatment commencement to until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months. ]
- Overall survival (OS) as defined as the time from first vaccination to date of death from any cause. [ Time Frame: From the date of treatment commencement to the date of death from any cause, whichever came first, assessed up to 48 months.. ]
- To demonstrate a MYB-specific immune response through epitope stimulation of PBMCs and assessment with CBA, FACS for IFN-γ and TNF-α production, and via the evaluation of changes in tumour microenvironment in pre- and post-treatment biopsies. [ Time Frame: Through study completion, an average of 48 months. ]
- To assess metabolic response, as assessed by FDG-PET scan. [ Time Frame: Week 4, at the time of disease progression and 4 weeks after treatment is ceased. ]
- The objective immune response as defined by achievement of a complete or partial response (irCR or irPR), based on irRECIST criteria. [ Time Frame: End of week 12. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03287427
|Contact: Jayesh Desai||+61 8559 email@example.com|
|Contact: Laura Gallettafirstname.lastname@example.org|
|Peter MacCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3000|
|Contact: Jayesh Desai +61 38559 7810 email@example.com|
|Principal Investigator:||Jayesh Desai||Peter MacCallum Cancer Centre, Australia|