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

Solid Tumor Clinical Trial

— KOSMOSII  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05525858
• Other study ID #: KCSG AL 22-09
• Status: Recruiting
• Start date: September 28, 2022
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: Seoul National University Bundang Hospital
• Contact: JEEHYUN KIM
• Phone: +82)070-4193-8602
• Email: kosmos2[@]kcsg.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Metastatic Cancer
• Neoplasms
• Solid Tumor

Intervention

Drug:
• Alectinib
ALK fusion or mutations, Mutations or amplification in any of the following: RET
• 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)
• 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
• 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
• 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
• Vemurafenib
BRAF_V600E/D/K/R mutations
• Bevacizumab + Erlotinib
FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board
• 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
• 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

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital	Korean Cancer Study Group, Roche Pharma AG

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	Progression-free survival	Progression-free survival in accordance with local clinical practice	12 months after treatment initiation (estimated average)
Secondary	Treatment duration	The period from the start of treatment to the end of treatment for any reason	12 months after treatment initiation (estimated average)
Secondary	1-year overall survival rate	Proportion of patients alive 1 year after study registration	12 months after treatment initiation (estimated average)
Secondary	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)