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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor; Metastatic Cancer; Advanced Solid Tumor
• Intervention / Treatment: Drug: Alectinib; Drug: Atezolizumab; Drug: Erlotinib; Drug: Trastuzumab + Pertuzumab; Drug: Trastuzumab emtansine; Drug: Vemurafenib; Drug: Bevacizumab + Erlotinib; Drug: Entrectinib; Drug: Pralsetinib

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

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Alectinib; ALK fusion or mutations, Mutations or amplification in any of the following: RET; Other Names: Alecensa; 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); Other Names: Tecentriq; 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; Other Names: Tarceva; 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; Other Names: Herceptin + Perjeta; 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; Other Names: Kadcyla; Drug: Vemurafenib; BRAF_V600E/D/K/R mutations; Other Names: Zelboraf; Drug: Bevacizumab + Erlotinib; FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board; Other Names: Avastin + Tarceva; 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; Other Names: Rozlytrek; 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; Other Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Assessed at 16 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	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	Progression-free survival in accordance with local clinical practice	12 months after treatment initiation (estimated average)
Treatment duration	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	Proportion of patients alive 1 year after study registration	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 )	12 months after treatment initiation (estimated average)

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Roche Pharma AG; Korean Cancer Study Group
• Investigators: Study Director: JEEHYUN KIM, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Kim SY, Kim JH, Kim TY, Park SR, Yoon S, Lee S, Lee SH, Kim TM, Han SW, Kim HR, Yun H, Lee S, Kim J, Choi YL, Choi KS, Chae H, Ryu H, Lee GW, Zang DY, Ahn JB. Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22-09. BMC Cancer. 2024 May 9;24(1):574. doi: 10.1186/s12885-024-12338-y.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 29, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Amides; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Sulfonamides; Sulfones; Quinazolines; Maytansine; Trastuzumab; Erlotinib Hydrochloride; Bevacizumab; Ado-Trastuzumab Emtansine; Vemurafenib; pertuzumab; atezolizumab; entrectinib; alectinib; pralsetinib
• Other Study ID Numbers: KCSG AL 22-09

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No