The TG01 Study With TG01/QS-21 Vaccine in Patients With High-risk Smouldering Multiple Myeloma and Multiple Myeloma

Inclusion criteria

• Male or female patients ≥ 18 years of age
• RAS mutation (KRAS/NRAS codon 12/13 mutation) detected on archival or fresh bone marrow material with VariantPlex Myeloid Panel
• Confirmed diagnosis of high-risk smoldering multiple myeloma (SMM) according to IMWG criteria (30) and high-risk criteria as listed up below OR confirmed diagnosis of multiple myeloma (MM) according to IMWG criteria and measurable disease following ≥

1 line of treatment

• In patients with high-risk SMM at least 2 of 3 following abnormalities, based on laboratory data obtained at screening must be fulfilled:

• Serum M-protein >20 g/L.
• Serum involved/uninvolved FLC ratio >20.
• BMPC >20%. OR presence of ≥10% BMPC and at least one of the following based on laboratory data obtained at screening:

• Serum M-protein ≥30 g/L (If IgA, IgA ≥20g/L)
• Serum involved/uninvolved FLC ratio ≥8 (but <100)
• Abnormal PC immunophenotype (≥95% of BMPCs are clonal) and reduction of ≥1uninvolved Ig isotype (Only IgG, IgA and IgM will be considered)
• Progressive increase in Serum M-protein level (evolving type of SMM) defined as an increase of Serum M-protein ≥10% in the last 12 months before enrolment in the study. This increase must be consistent from one to another sample (i.e., no decrease observed between 2 increased Serum M-protein values)
• Both high-risk SMM and MM patients must have evidence of measurable disease in accordance with IMWG criteria
• If patient with MM was eligible for ASCT, ASCT must have been performed, and patients cannot be enrolled until 3 months after ASCT
• Patient should not be expected to require immediate, subsequent line of treatment for at least 2 months
• Patient has not had reduction of clonal plasma cell markers for last two cycles (last two months if off treatment). If a patient had no reduction during the last two cycles of induction before ASCT, the patient can be enrolled, provided 3 months after ASCT
• Following ASCT, the patient cannot be enrolled without having tried lenalidomide maintenance given at standard doses for at least two cycles, if the clonal markers had a reduction during the last 2 cycles of induction treatment. Lenalidomide will be stopped when entering the study
• ECOG performance status 0-1
• Female patients of child-bearing potential (FCBP) must have negative serum pregnancy test at Screening and agree to use a highly effective method of contraception during treatment and for 3 months following last dose of drug.
• Male patients must use an effective barrier method of contraception during treatment and for 3 months following the last dose if sexually active with a FCBP.
• Ability to provide written informed consent and can understand and comply with the requirements of the study

Exclusion criteria

• Pregnant or lactating women or women without a pregnancy test at baseline (postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential)
• Medical conditions such as but not limited to:

• Any uncontrolled infection
• Uncontrolled cardiac failure classification III or IV (NYHA)
• Uncontrolled systemic and gastro-intestinal inflammatory conditions
• History of adverse reactions to vaccines
• Active malignancy with worse prognosis than multiple myeloma
• Likely to require treatment intervention for multiple myeloma within two months of start of treatment with TG01/QS-21
• Known history of positive tests for HIV/AIDS, hepatitis B or C
• Planned to receive yellow fever or other live (attenuated) vaccines during the course of study
• Known hypersensitivity to QS-21.
• Only participants who are able to consent will be included in the study.