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

Launched by OSLO UNIVERSITY HOSPITAL · May 2, 2023

Keywords

ClinConnect Summary

The TG01 Study is a clinical trial looking at a new vaccine called TG01/QS-21 for patients with high-risk smoldering multiple myeloma or multiple myeloma. The main goals of this study are to see if the vaccine is safe and if it helps patients respond better to treatment, live longer, and delay the need for further treatment. Participants in this trial will receive the TG01/QS-21 vaccine 12 times over 52 weeks, starting with doses every two weeks for the first three months and then every eight weeks afterward.

To be eligible for this study, patients must be at least 18 years old and have a specific mutation (called KRAS or NRAS) in their bone marrow. They should also have a confirmed diagnosis of either high-risk smoldering multiple myeloma or multiple myeloma with measurable disease. Participants will need to meet certain health criteria and will be monitored for any side effects or responses to the vaccine throughout the study. This trial is currently recruiting participants, and those considering joining should discuss it with their healthcare team to understand more about what to expect.

Gender

ALL

Eligibility criteria

• 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.