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

Recruiting

• Conditions: Solid Tumor; Advanced Solid Tumor; Metastatic Cancer
• Interventions: Drug: Alectinib; Drug: Atezolizumab; Drug: Erlotinib; Drug: Trastuzumab + Pertuzumab; Drug: Trastuzumab emtansine; Drug: Vemurafenib; Drug: Bevacizumab + Erlotinib; Drug: Entrectinib; Drug: Pralsetinib

• Registration Number: NCT05525858
• Lead Sponsor: Seoul National University Bundang Hospital

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)

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 Timeline

• Study First Submitted: 2022-08-29
• Study First Submitted QC: 2022-08-30
• Study First Posted: 2022-09-02
• Study Start: 2022-09-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-27
• Primary Completion: 2026-09
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Trastuzumab + Pertuzumab	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Bevacizumab + Erlotinib	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Alectinib	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Atezolizumab	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Trastuzumab emtansine	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Erlotinib	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Vemurafenib	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Entrectinib	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.
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)	Pralsetinib	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.

Primary Outcome Measures

Name	Time	Method
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	12 months after treatment initiation (estimated average)	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.
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	Assessed at 16 weeks of treatment	Percentage of patients achieving response defined as CR/PR/SD at 16 ± 2 weeks reported by site physician

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	12 months after treatment initiation (estimated average)	Progression-free survival in accordance with local clinical practice
To evaluate safety of molecular profiling guided therapies	12 months after treatment initiation (estimated average)	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 )
Objective response rate	12 months after treatment initiation (estimated average)	The proportion of patients who obtained CR/PR as the best response according to the RECIST 1.1 criteria
Treatment duration	12 months after treatment initiation (estimated average)	The period from the start of treatment to the end of treatment for any reason
1-year overall survival rate	12 months after treatment initiation (estimated average)	Proportion of patients alive 1 year after study registration

Trial Locations

Locations (32)

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

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