Clinical Trial Finder

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: 1.

Serum M-protein >20 g/L. 2. Serum involved/uninvolved FLC ratio >20. 3. 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: 1.

Any uncontrolled infection. 2. Uncontrolled cardiac failure classification III or IV (NYHA) 3. Uncontrolled systemic and gastro-intestinal inflammatory conditions. 4. 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.

Arms

Experimental: TG01

TG01 is a sterile lyophilizate consisting of a mixture of seven peptides. The finished product is a white powder for injection, consisting only of the active substances containing 2.1 mg of peptides (individual peptides comprising 0.3 mg each). The lyophilizate is to be reconstituted with QS-21 for injection before use. QS-21 is a naturally occurring saponin molecule purified from the South American tree Quillaja saponaria Molina. QS-21 Solution is supplied in a 2 mL CZ resin vial as a sterile, solution in PBS (phosphate buffered saline) at a concentration of 0.5 mg/mL QS-21 (500 mcg/mL) with each vial containing 0.7 mL intended single use only. The vaccine will be given subcutaneously Treatment consists of 12 doses TG01/QS-21 vaccine given every 2 weeks in the first 12 weeks, followed by every 8 weeks until week 52. TG01 dose 0.7 mg dose and QS-21 50 ug.

Interventions

Biological: - TG01

All participants will receive the same treatment as described under arm