Vaccination with TG01/QS-21 for patients with high-risk smoldering multiple myeloma and multiple myeloma

A Phase 1/Phase 2 Study to Investigate Safety, Tolerability and Efficacy With TG01/QS-21 Vaccine Administration in Patients With Confirmed KRAS or NRAS Codon 12/13 Mutation and High-risk Smoldering Multiple Myeloma or Multiple Myeloma and Evidence of Measurable Disease ≥ 1 Line of Treatment

This study is testing a new vaccine to see if it can help people with high-risk smoldering multiple myeloma or multiple myeloma who have certain gene mutations feel better and live longer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oslo University Hospital (Academic / other)
• Locations: 1 site (Oslo, Oslo)
• Trial ID: NCT05841550 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety, tolerability, and efficacy of the TG01/QS-21 vaccine in patients with high-risk smoldering multiple myeloma or multiple myeloma who have specific KRAS or NRAS mutations. Participants will receive 12 doses of the vaccine over 52 weeks, with doses administered every two weeks initially, followed by every eight weeks. The study will assess various outcomes, including overall response rate, overall survival, progression-free survival, and immunological response to the vaccine. The trial is designed to provide insights into the potential benefits of this vaccination approach for these patient populations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed high-risk smoldering multiple myeloma or multiple myeloma and specific RAS mutations.

Not a fit: Patients without the specified KRAS or NRAS mutations or those with low-risk smoldering multiple myeloma may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccination could improve treatment outcomes and survival rates for patients with high-risk smoldering multiple myeloma and multiple myeloma.

How similar studies have performed: While there have been studies exploring immunotherapy in multiple myeloma, the specific approach of using TG01/QS-21 vaccination in this context is novel.

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.

Where this trial is running

Oslo, Oslo

• Oslo Myeloma Center — Oslo, Oslo, Norway (Recruiting)

Study contacts

• Principal investigator: Fredik Schjesvold, MD PhD — Oslo Myeloma Center, Oslo University Hospital
• Study coordinator: Hanne Norseth, MD

Conditions Multiple Myeloma; Smoldering Multiple Myeloma