NCT05525858

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

KOrean Precision Medicine Networking Group Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 1,000 (estimated)
• Sponsor: Seoul National University Bundang Hospital · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

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)

Detailed description

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

Conditions

• Solid Tumor
• Advanced Solid Tumor
• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	Alectinib	ALK fusion or mutations, Mutations or amplification in any of the following: RET
DRUG	Atezolizumab	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)
DRUG	Erlotinib	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
DRUG	Trastuzumab + Pertuzumab	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
DRUG	Trastuzumab emtansine	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
DRUG	Vemurafenib	BRAF\_V600E/D/K/R mutations
DRUG	Bevacizumab + Erlotinib	FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board
DRUG	Entrectinib	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
DRUG	Pralsetinib	RET fusion or mutations; CCDC6 RET, RET V804L, RET V804M, RET M918T, KIF5B-RET, RET C634W or approved by the KOSMOS Molecular Tumor Board

Timeline

• Start date: 2022-09-28
• Primary completion: 2026-09-01
• Completion: 2027-03-01
• First posted: 2022-09-02
• Last updated: 2025-04-27

Locations

32 sites across 1 country: South Korea