Clinical trial NCT05841550: The TG01 Study With TG01/QS-21 Vaccine in Patients With High-risk Smouldering Multiple Myeloma and Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Smoldering Multiple Myeloma
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Targovax ASA
First posted: 2023-05-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the safety, tolerability, and efficacy of TG01 vaccination in patients with KRAS or NRAS mutation on codon 12/13 mutation who has multiple myeloma or high-risk smoldering multiple myeloma. The main question it aims to answer are:

Is TG01/QS-21 vaccination safe and tolerable for this patient group? Is TG01/QS-21 vaccination treatment efficient in this group in terms of increased overall response rate, overall survival rate, progression-free survival, and time til next treatment? Is there an immunological response to the vaccine? Participants will be given TG01/QS-21 vaccination treatment. Treatment consists of 12 doses of TG01/QS-21 vaccine given every two weeks in the first 12 weeks, followed by every eight weeks until week 52.


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.

Primary outcomes:
measure: Percentage of participants with adverse events (AEs)
timeFrame: Baseline until 30 days after last dose of study drug, up to approximately 3 years
measure: Percentage of participants discontinuing treatment secondary to treatment-related adverse events
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Number of patients with Progression Free Survival (PFS)
timeFrame: Baseline to 11 years
measure: Concentration of TG01-specific T-cell specific cytokine production
timeFrame: Baseline until end of study, assessed up to 11 years
measure: Overall response rate per patient
timeFrame: Baseline to approximately 3 years
measure: Overall Survival (OS) per patient
timeFrame: Baseline until the end of study, assessed up to 11 years
measure: Time to next treatment (TTNT) per patient
timeFrame: Baseline until the end of study, assessed up to 11 years
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo Myeloma Center
Study officials:
affiliation: Oslo Myeloma Center, Oslo University Hospital
name: Fredik Schjesvold, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: