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)
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
Study Type
OBSERVATIONAL
Enrollment
1,000
ALK fusion or mutations, Mutations or amplification in any of the following: RET
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)
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
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
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
BRAF\_V600E/D/K/R mutations
FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board
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
RET fusion or mutations; CCDC6 RET, RET V804L, RET V804M, RET M918T, KIF5B-RET, RET C634W or approved by the KOSMOS Molecular Tumor Board
Soonchunhyang University Hospital Bucheon
Bucheon-si, South Korea
RECRUITINGChungbuk National University Hospital
Chungju, South Korea
RECRUITINGKeimyung University Dongsan Hospital
Daegu, South Korea
RECRUITINGKyungpook National University Chilgok Hospital
Daegu, South Korea
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
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.
Time frame: 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
Percentage of patients achieving response defined as CR/PR/SD at 16 ± 2 weeks reported by site physician
Time frame: Assessed at 16 weeks of treatment
Objective response rate
The proportion of patients who obtained CR/PR as the best response according to the RECIST 1.1 criteria
Time frame: 12 months after treatment initiation (estimated average)
Progression-free survival
Progression-free survival in accordance with local clinical practice
Time frame: 12 months after treatment initiation (estimated average)
Treatment duration
The period from the start of treatment to the end of treatment for any reason
Time frame: 12 months after treatment initiation (estimated average)
1-year overall survival rate
Proportion of patients alive 1 year after study registration
Time frame: 12 months after treatment initiation (estimated average)
To evaluate safety of molecular profiling guided therapies
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 )
Time frame: 12 months after treatment initiation (estimated average)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Yeungnam University Medical Center
Daegu, South Korea
RECRUITINGChungnam National University Hospital
Daejeon, South Korea
RECRUITINGNational Cancer Center
Goyang, South Korea
RECRUITINGChonnam National University Hwasun Hospital
Hwasun, South Korea
RECRUITINGGachon University Gil Medical Center
Incheon, South Korea
RECRUITINGThe Catholic University of Korea, Incheon St. Mary's Hospital
Incheon, South Korea
RECRUITING...and 22 more locations