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

NCT03287427 | Completed Phase 1 DMC

• 1 other identifier: MYPHISMO
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Adenoid Cystic Carcinoma

Keywords

Advanced; Metastatic

Outcome Measures

Primary Outcomes (1)

• 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).

  End of Week 6

Secondary Outcomes (9)

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

  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.

  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.

  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.

  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.

  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.

Study Arms (1)

TetMYB Vaccine & BGB-A317

EXPERIMENTAL

Drug: TetMYB Vaccine; Drug: BGB-A317

Interventions

TetMYB Vaccine DRUG

Weekly intra-dermal injections of either 0.1mg, 0.5mg or 1.0mg on day 1 for week 1 to week 6.

TetMYB Vaccine & BGB-A317

BGB-A317 DRUG

3 weekly IV injections of 200mg commencing from Week 4.

TetMYB Vaccine & BGB-A317

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 years or older at screening.
• Patients with advanced/metastatic colorectal or adenoid cystic carcinoma; for which no effective standard therapy is available.
• 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.
• Measurable disease as per irRECIST criteria 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Life expectancy greater than 3 months.
• 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)
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• 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
• 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.
• 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.
• Active Hepatitis C: Patients positive for Hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• History of adverse reactions to peptide vaccines.
• Patients who are pregnant or lactating.
• Has received an investigational drug within 4 weeks prior to first dose of study drug, or unless other has been agreed with the SSC.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Related Publications (1)

• Pham T, Pereira L, Roth S, Galletta L, Link E, Akhurst T, Solomon B, Michael M, Darcy P, Sampurno S, Heriot A, Ramsay R, Desai J. First-in-human phase I clinical trial of a combined immune modulatory approach using TetMYB vaccine and Anti-PD-1 antibody in patients with advanced solid cancer including colorectal or adenoid cystic carcinoma: The MYPHISMO study protocol (NCT03287427). Contemp Clin Trials Commun. 2019 Jul 10;16:100409. doi: 10.1016/j.conctc.2019.100409. eCollection 2019 Dec.

  PMID: 31650066 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Adenoid Cystic; Neoplasm Metastasis

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jayesh Desai

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 19, 2017
• Study Start: August 22, 2018
• Primary Completion: December 14, 2022
• Study Completion: December 14, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

AU (1)