KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

Sponsor
Seoul National University Bundang Hospital
Study ID
NCT05525858
Status
Recruiting
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Conditions

  • Advanced Solid Tumor
  • Metastatic Cancer
  • Solid Tumor

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Alectinib — DRUG
    ALK fusion or mutations, Mutations or amplification in any of the following: RET
  • Atezolizumab — DRUG
    MSI high status by any method Or Any mutation in any of these genes: MLH1 or MSH2 or MSH6 or PMS2 or EPCAM Or Any of the following mutations in POLE: R150X, P286R, P286H, S297F, Y298fs, F367S, V411, L424V, P436R, S459F, R665W, L698fs, R762W, R1519C, R1826W, D316H, D316G, R409W, L474P Or Any of the following mutations in POLD1: P112fs, A930fs, S478N Or Any mutation in the following: POLE not listed above, POLD1 not listed above, POLD2, POLD3, POLD4, POLQ or PRKDC Or Any loss of function mutations in BRCA1, BRCA2, ATM, MSH3, PMS1, MLH3, EXO1, RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, RPA1, PRA2, PRA3, PRA4, or SSBP1 High tumor mutational burden decided by KOSMOS-II MTB (TMB ≥20/Mb in local NGS or if 10-20/Mb, confirmed by central NGS te sting)
  • Erlotinib — DRUG
    EGFR Exon 19 deletions in the region E746\_E759; Any of the following EGFR mutations: E709A, E709G, E709K, E884K, G719A, G719C, G719S, L858R, L861Q, L833V, S768I
  • Trastuzumab + Pertuzumab — DRUG
    ERBB2 amplification, or over-expression; or presence of any of the following ERBB2 mutations: G309A, G309E, S310F, S310Y, R678Q, I655V, D769H, D769Y, L755S, p.L75 5\_T759del, I767M, V777L, E321G, R896C; P780ins; delL755-T759 ERBB2 amplification or approved by the KOSMOS Molecular Tumor Board
  • Trastuzumab emtansine — DRUG
    ERBB2 amplification, or over-expression; or presence of any of the following ERBB2 mutations: G309A, G309E, S310F, S310Y, R678Q, I655V, D769H, D769Y,L755S, p.L75 5\_T759del, I767M, V777L, E321G, R896C; P780ins; delL755-T759 ERBB2 oncogenic mutations; G152V, X215\_splice, D277Y, G292C, N302K, V308M, G309A, S310F, S310Y, S244C, L651V, V659E, G660D, R678Q, V697L, G727A, T733I, L755A, L755P, L755S, D769H, D769Y, A775\_G776insSVMA, A775\_G776insYVMA (i.e.,Y772\_A775dup,M774\_A775insAYVME 770delinsEAYVM), G776\_V777 \> AVCV, G776\_V777 \> AVGCV, G776\_V777 \> VCV, G776\_V777insVC, G776C, G776delinsLCT, G776L, G776dleinsVC, G776L777\_G778insC, V777L, V777M, G778\_Y779insGSP, P780\_Y781insGSP (i.e.,G778\_P780dup), L786V, N813D, R840W, V842I, T862A, R896G, E1021Q or approved by the KOSMOS Molecular Tumor Board
  • Vemurafenib — DRUG
    BRAF\_V600E/D/K/R mutations
  • Bevacizumab + Erlotinib — DRUG
    FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board
  • Entrectinib — DRUG
    ROS1 gene fusion using either a fluo rescence in situ hybridization (FISH) or next-generation sequencing (NGS) or approved by the KOSMOS Molecular Tumor Board
  • Pralsetinib — DRUG
    RET fusion or mutations; CCDC6 RET, RET V804L, RET V804M, RET M918T, KIF5B-RET, RET C634W or approved by the KOSMOS Molecular Tumor Board

Study Details

A national, prospective, multi-center, open-label, multi-cohort study comprised of a framework to screen patients for actionable targets and evaluation of molecular profiling guided therapy recommended by MTB based on genomic alterations using targeted and/or immunotherapies outside of the approved indications via local clinical practice (Tier 1 \& 2) and clinical trials (Tier 3)

Key Dates

Start date
Sep 28, 2022
Status verified
Apr 2025
Primary completion
Sep 30, 2026
Completion
Mar 31, 2027

Study Design

Enrollment
1,000 participants (estimated)

Arms

  • Arm: Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)
    If there are no drugs available under current regulation or patients are not feasible to any clinical trials, and If tumors have actionable genetic alterations and approved drug in any indications but tumor type is not indicative, the MTB may recommend one of KOSMOS-II drugs, therapeutic use of investigational products.
  • Arm: Tier 2: Alternative treatments
    If there are no KOSMOS-II drugs (Tier 1) or clinical trials (Tier 3) appropriate for patients, the MTB may recommend alternative treatment options (e.g., conventional therapy, radiotherapy, or supportive care).
  • Arm: Tier 3: Clinical trial
    If patient is eligible for clinical trials matched for actionable genomic alterations found in NGS testing, the MTB will recommend enrollment to clinical trials.

Primary Outcome Measure

To evaluate the feasibility of molecular profiling guided therapies (MGT) based on genomic alterations in patients with advanced solid tumors in terms of the proportion of receipt of the treatment [ Time Frame: 12 months after treatment initiation (estimated average) ]

Central Contacts

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