Health TrialsbyHealthPanel

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

ConditionsSolid TumorAdvanced Solid TumorMetastatic Cancer
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age19+
SponsorSeoul National University Bundang Hospital

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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.

Disqualifiers

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

Trial 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

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Alectinib

    Drug

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

  • 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)

  • 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

  • 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

  • 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

  • Vemurafenib

    Drug

    BRAF\_V600E/D/K/R mutations

  • Bevacizumab + Erlotinib

    Drug

    FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board

  • 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

  • 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

Treatment groups

1,000 Participants
are divided into 3 treatment groups
Group A: Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)9 interventions
Group B: Tier 2: Alternative treatments0 interventions
Group C: Tier 3: Clinical trial0 interventions

Trial outcomes

Primary outcomes

1

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)
2

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

Secondary outcomes

1

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)
2

Progression-free survival

Progression-free survival in accordance with local clinical practice

Time frame
12 months after treatment initiation (estimated average)
3

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)
4

1-year overall survival rate

Proportion of patients alive 1 year after study registration

Time frame
12 months after treatment initiation (estimated average)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Seoul National University Bundang Hospital

Lead sponsor

Korean Cancer Study Group

Collaborator

Roche Pharma AG

Collaborator

Source ClinicalTrials.gov
Apply now