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

NCT05525858 | Recruiting

• 1 other identifier: KCSG AL 22-09
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 32

Brief 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)

Conditions

Solid Tumor; Advanced Solid Tumor; Metastatic Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Objective response rate

  12 months after treatment initiation (estimated average)

• Progression-free survival

  12 months after treatment initiation (estimated average)

• Treatment duration

  12 months after treatment initiation (estimated average)

• 1-year overall survival rate

  12 months after treatment initiation (estimated average)

• To evaluate safety of molecular profiling guided therapies

  12 months after treatment initiation (estimated average)

Study Arms (3)

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; Drug: Atezolizumab; Drug: Erlotinib; Drug: Trastuzumab + Pertuzumab; Drug: Trastuzumab emtansine; Drug: Vemurafenib; Drug: Bevacizumab + Erlotinib; Drug: Entrectinib; Drug: Pralsetinib

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.

Interventions

Alectinib DRUG

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

Also known as: Alecensa

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Atezolizumab DRUG

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)

Also known as: Tecentriq

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Erlotinib DRUG

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

Also known as: Tarceva

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Trastuzumab + Pertuzumab DRUG

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

Also known as: Herceptin + Perjeta

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Trastuzumab emtansine DRUG

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

Also known as: Kadcyla

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Vemurafenib DRUG

BRAF\_V600E/D/K/R mutations

Also known as: Zelboraf

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Bevacizumab + Erlotinib DRUG

FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board

Also known as: Avastin + Tarceva

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Entrectinib DRUG

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

Also known as: Rozlytrek

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Pralsetinib DRUG

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

Also known as: Gavreto

Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead
• Korean Cancer Study Group: collaborator
• Roche Pharma AG: collaborator

Study Sites (32)

Soonchunhyang University Hospital Bucheon

Bucheon-si, South Korea

RECRUITING

Chungbuk National University Hospital

Chungju, South Korea

RECRUITING

Keimyung University Dongsan Hospital

Daegu, South Korea

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, South Korea

RECRUITING

Yeungnam University Medical Center

Daegu, South Korea

RECRUITING

Chungnam National University Hospital

Daejeon, South Korea

RECRUITING

National Cancer Center

Goyang, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, South Korea

RECRUITING

The Catholic University of Korea, Incheon St. Mary's Hospital

Incheon, South Korea

RECRUITING

Jeonbuk National University Hospital

Jeonju, South Korea

RECRUITING

Gyeongsang National University Hospital

Jinju, South Korea

RECRUITING

Dong-A University Hospital

Pusan, South Korea

RECRUITING

Cha University Bundang Medical Center

Seongnam, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Chung-ang University Hospital

Seoul, South Korea

RECRUITING

Ewha womans university Mokdong Hospital

Seoul, South Korea

RECRUITING

Gangbuk Samsung Hospital

Seoul, South Korea

RECRUITING

Hanyang University Hospital

Seoul, South Korea

TERMINATED

Korea University Anam Hospital

Seoul, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

The Catholic University of Korea, Seoul ST. Mary's Hospital

Seoul, South Korea

RECRUITING

The Catholic University of Korea, Yeouido St. Mary's Hospital

Seoul, South Korea

RECRUITING

Yonsei Cancer Hospital

Seoul, South Korea

RECRUITING

Ajou University Hospital

Suwon, South Korea

RECRUITING

The Catholic University of Korea, ST. Vincent's Hospital

Suwon, South Korea

RECRUITING

Ulsan University Hospital

Ulsan, South Korea

RECRUITING

Wonju Severance Christian Hospital

Wŏnju, South Korea

RECRUITING

Pusan National University Yangsan Hospital

Yangsan, South Korea

RECRUITING

Related Publications (1)

• 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.

  PMID: 38724991 DERIVED

Biospecimen

Retention: NONE RETAINED

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.

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

alectinib; atezolizumab; Erlotinib Hydrochloride; Trastuzumab; pertuzumab; Ado-Trastuzumab Emtansine; Vemurafenib; Bevacizumab; entrectinib; pralsetinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles

Study Officials

• JEEHYUN KIM

  Seoul National University Bundang Hospital

  STUDY DIRECTOR

Central Study Contacts

JEEHYUN KIM

CONTACT

+82)070-4193-8602; kosmos2@kcsg.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 2, 2022
• Study Start: September 28, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

KR (32)