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KPMNG-undersøgelse af molekylær profileringsguidet terapi baseret på genomiske ændringer i avancerede solide tumorer II (KOSMOSII)

29. september 2026 opdateret af: Jee Hyun Kim, Seoul National University Bundang Hospital

KOrean Precision Medicine Networking Group Studie af molekylær profileringsguidet terapi baseret på genomiske ændringer i avancerede solide tumorer II

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)

Studieoversigt

Status

Aktiv, ikke rekrutterende

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

A. The KOSMOS-II study will recruit locally advanced or metastatic solid tumor patients who had disease progression on standard first line anti-cancer treatment and/or has no standard treatment option, in order to prove MTB value to guide treatment within local clinical practice.

B. After site physicians confirm that NGS results of patients are available, they preliminarily decide initial treatment before MTB submission and collect informed consent form, and then patients can register to the KOSMOS-II study. Site physicians upload patients' clinical, pathologic, and genomic data for MTB submission. If site physician cannot determine initial treatment before MTB, site physician can record 'initial treatment cannot be determined' and can register the patient for MTB.

C. MTB records its treatment recommendations within available drugs list based on uploaded data, then site physicians make a final treatment decision, after informing patient about MTB decision and assessment of patients' final health status and preference.

D. Patients who have insufficient genomic information from their NGS results (e.g., lack of variant calling format file or uninterpretable reports) or who are candidates of immunotherapy will submit their tissue and/or blood, for central NGS testing and exploratory biomarker analysis.

E. Recommended treatment option There are three different options including (1) Tier 1: Therapeutic use of investigational products (KOSMOS-II drugs), (2) Tier 2: alternative treatment options, and (3) Tier 3: clinical trials

Undersøgelsestype

Observationel

Tilmelding (Faktiske)

1000

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Bucheon-si, Sydkorea
        • Soonchunhyang University Hospital Bucheon
      • Chungju, Sydkorea
        • Chungbuk National University Hospital
      • Daegu, Sydkorea
        • Keimyung University Dongsan Hospital
      • Daegu, Sydkorea
        • Kyungpook National University Chilgok Hospital
      • Daegu, Sydkorea
        • Yeungnam University Medical Center
      • Daejeon, Sydkorea
        • Chungnam National University Hospital
      • Goyang, Sydkorea
        • National Cancer Center
      • Hwasun, Sydkorea
        • Chonnam National University Hwasun Hospital
      • Incheon, Sydkorea
        • Gachon University Gil Medical Center
      • Incheon, Sydkorea
        • The Catholic University of Korea, Incheon St. Mary's Hospital
      • Jeonju, Sydkorea
        • Jeonbuk National University Hospital
      • Jinju, Sydkorea
        • Gyeongsang National University Hospital
      • Pusan, Sydkorea
        • Dong-A University Hospital
      • Seongnam, Sydkorea
        • Cha University Bundang Medical Center
      • Seongnam, Sydkorea
        • Seoul National University Bundang Hospital
      • Seoul, Sydkorea
        • Asan Medical Center
      • Seoul, Sydkorea
        • Korea University Anam Hospital
      • Seoul, Sydkorea
        • Korea University Guro Hospital
      • Seoul, Sydkorea
        • Samsung Medical Center
      • Seoul, Sydkorea
        • Seoul National University Hospital
      • Seoul, Sydkorea
        • The Catholic University of Korea, Yeouido St. Mary's Hospital
      • Seoul, Sydkorea
        • Gangbuk Samsung Hospital
      • Seoul, Sydkorea
        • Hanyang University Hospital
      • Seoul, Sydkorea
        • Chung-ang University Hospital
      • Seoul, Sydkorea
        • Ewha womans university Mokdong Hospital
      • Seoul, Sydkorea
        • The Catholic University of Korea, Seoul ST. Mary's Hospital
      • Seoul, Sydkorea
        • Yonsei Cancer Hospital
      • Suwon, Sydkorea
        • Ajou University Hospital
      • Suwon, Sydkorea
        • The Catholic University of Korea, ST. Vincent's Hospital
      • Ulsan, Sydkorea
        • Ulsan University Hospital
      • Wŏnju, Sydkorea
        • Wonju Severance Christian Hospital
      • Yangsan, Sydkorea
        • Pusan National University Yangsan Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

19 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

Histologically proven locally advanced or metastatic solid tumor patients with disease progression on standard first line anti-cancer treatment and/or has no standard treatment option

Beskrivelse

Inclusion Criteria:

  • 19 years of age or older

  • Histologically proven locally advanced or metastatic solid tumors*** who showed disease progression on standard first line anti-cancer treatment and/or has no standard treatment option

    *** very rare diseases without standard treatment option which form solid mass, such as Erdheim Chester disease can be enrolled after KOSMOS MTB approval

  • A genomic test results must be available in a MFDS-accredited for laboratories offering service, or in part of clinical trial/study or other commercial labs approved and certified by regulatory bodies compatible with MFDS, such as CLIA. A genomic test can be conducted with tumor tissue as well as plasma circulating tumor DNA.

    1. Results from genomic profiling tests performed after diagnosis with metastatic/advanced disease to registration are acceptable. NGS results performed within three years prior to registration are preferred. Those patients with NGS results from primary tumor or more than 3 years prior to enrollment can be registered and whether NGS data is acceptable will be subject to MTB decision.
    2. NGS panels should be i. Tested in a lab that is accredited by one or more quality assurance program (e.g., Korean Institute of Genomic Testing Evaluation, The Korean Society of Pathologists, Korean Society for Laboratory Medicine, Korea Laboratory Accreditation Scheme, etc.) ii. Patients who have insufficient genomic information from their NGS results (e.g., lack of variant calling format file or uninterpretable reports) or who are candidates of immunotherapy will submit their tissue and/or blood, for central NGS testing and exploratory biomarker analysis.
  • Ability to understand and the willingness to sign a written informed consent document

  • Life expectancy of at least 12 weeks

  • Adequate recovery from most recent systemic or local treatment for cancer.

Exclusion Criteria:

  • Patients receiving any anti-cancer treatment (local treatment, chemotherapy, immunotherapy, targeted therapy) within 2 weeks prior to the start of study treatment
  • Any clinical condition, according to the opinion of site physicians, which makes molecular profiling guided therapy not at the best interest of the participating patient.
  • Patients who have ongoing toxicities of ≥ CTCAE 2, other than peripheral neuropathy, related to previous anti-cancer treatment. Patients with ongoing peripheral neuropathy of ≥ CTCAE 3 will be excluded. Laboratory abnormalities ≥ CTCAE 2 considered as not clinically significant by the study physician will be allowed.
  • Pregnant or breastfeeding, or intending to become pregnant during the study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Observationsmodeller: COHORT
  • Tidsperspektiver: PROSPECTIVE

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
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.

ALK fusion or mutations, Mutations or amplification in any of the following: RET

Andre navne:
  • Alecensa

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)

Andre navne:
  • Tecentriq

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

Andre navne:
  • Tarceva

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

Andre navne:
  • Herceptin + Perjeta

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

Andre navne:
  • Kadcyla

BRAF_V600E/D/K/R mutations

Andre navne:
  • Zelboraf

FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board

Andre navne:
  • Avastin + Tarceva

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

Andre navne:
  • Rozlytrek

RET fusion or mutations; CCDC6 RET, RET V804L, RET V804M, RET M918T, KIF5B-RET, RET C634W or approved by the KOSMOS Molecular Tumor Board

Andre navne:
  • Gavreto
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).

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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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
Tidsramme: 12 months after treatment initiation (estimated average)

Percentage of patients who receive molecular profiling guided therapy as recommended by MTB, either in therapeutic use of investigational products (KOSMOS-II drugs), alternative treatment, or clinical trial.

12 months after treatment initiation (estimated average)
To evaluate the effectiveness of molecular profiling guided therapies in terms of clinical benefit rate (CR/PR/SD beyond 16 +/- 2 weeks) in Tier 1* population
Tidsramme: Assessed at 16 weeks of treatment

Percentage of patients achieving response defined as CR/PR/SD at 16 ± 2 weeks reported by site physician

Assessed at 16 weeks of treatment

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Objective response rate
Tidsramme: 12 months after treatment initiation (estimated average)

The proportion of patients who obtained CR/PR as the best response according to the RECIST 1.1 criteria

12 months after treatment initiation (estimated average)
Progression-free survival
Tidsramme: 12 months after treatment initiation (estimated average)

Progression-free survival in accordance with local clinical practice

12 months after treatment initiation (estimated average)
Treatment duration
Tidsramme: 12 months after treatment initiation (estimated average)

The period from the start of treatment to the end of treatment for any reason

12 months after treatment initiation (estimated average)
1-year overall survival rate
Tidsramme: 12 months after treatment initiation (estimated average)

Proportion of patients alive 1 year after study registration

12 months after treatment initiation (estimated average)
To evaluate safety of molecular profiling guided therapies
Tidsramme: 12 months after treatment initiation (estimated average)

The incidence of serious adverse events will be calculated among the adverse events in patients with Tier 1 and Tier 3. ( based on NCI-CTCAE v5.0 )

12 months after treatment initiation (estimated average)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Studieleder: JEEHYUN KIM, Seoul National University Bundang Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

28. september 2022

Primær færdiggørelse (Anslået)

31. marts 2027

Studieafslutning (Anslået)

31. marts 2027

Datoer for studieregistrering

Først indsendt

29. august 2022

Først indsendt, der opfyldte QC-kriterier

30. august 2022

Først opslået (Faktiske)

2. september 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

30. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

29. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .