Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Trastuzumab

Bevacizumab

Atezolizumab

Alectinib

Pertuzumab

Ado-Trastuzumab Emtansine

Pralsetinib

Entrectinib

Erlotinib Hydrochloride

Vemurafenib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tyrosine

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.

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).

If patient is eligible for clinical trials matched for actionable genomic alterations found in NGS testing, the MTB will recommend enrollment to clinical trials.

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

Erlotinib

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 + 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 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

Trastuzumab emtansine

FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board

Bevacizumab + Erlotinib

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

JEEHYUN KIM

Jina Yun

Yae-Won Yang

Keon-Uk Park

In-Hee Lee

Sung-Ae Koh

Hye-won Ryu

Yeong-ju Lee

Sang Hee Cho

Hee-Kyung Ahn

Jang-Ho Cho

So-Yeon Jeon

Gyeong-Won Lee

Seok-Jae Huh

Beo-Deul Kang

Jee Hyun Kim

Min-Hee Ryu

In-Gyu Hwang

Kyung-Eun Lee

Dong-Hoe Koo

Suk-Joong Oh

Soo-Hyeon Lee

Eunju Kang

Hyun-Ae Jung

Tae-Yong Kim

Se-Jun Park

In-Sook Woo

Min-Kyu Jung

Mi-Sun Ahn

Ho-Jung An

Hyeon-Su Im

Seung-Taek Lim

So-Yeon Oh

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

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.

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

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.

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

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

Progression-free survival in accordance with local clinical practice

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

Proportion of patients alive 1 year after study registration

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 )

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II	NCT05525858	Solid Tumor Advanced Solid ... Metastatic Canc...	Alectinib Atezolizumab Erlotinib Trastuzumab + P... Trastuzumab emt... Vemurafenib Bevacizumab + E... Entrectinib Pralsetinib	19 Years -	Seoul National University Bundang Hospital
KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II	NCT05525858	Solid Tumor Advanced Solid ... Metastatic Canc...	Alectinib Atezolizumab Erlotinib Trastuzumab + P... Trastuzumab emt... Vemurafenib Bevacizumab + E... Entrectinib Pralsetinib	19 Years -	Seoul National University Bundang Hospital

Spots Global Cancer Trial Database for bevacizumab + erlotinib