Master Protocol for Basket Clinical Trials of Targeted Therapies Based on Proteome and Whole Exome Sequencing Screening in Patients With Advanced Solid Tumors

NCT07891169 | Active Not Recruiting

• 2 other identifiers: NCC2024-030224H1640
• Study Type: interventional
• Target: 2,800
• Locations: 1 country
• Sites: 2

Brief Summary

Study Overview This study evaluates a proteogenomic screening platform to identify precise therapeutic targets for patients with advanced solid tumors. While traditional precision medicine relies on DNA sequencing (genomics), this research adds protein analysis (proteomics) to better understand how cancer cells function and respond to treatment.

• Identify active signaling networks that DNA testing alone might miss.
• Evaluate the feasibility and cost-effectiveness of this integrated platform compared to traditional methods.
• Help match patients to the most effective targeted therapies through a "Basket Trial" framework, where treatment is based on molecular signatures rather than where the cancer started in the body.
• Target Population
• Adults (19 years and older) with histologically confirmed metastatic or locally advanced solid tumors.
• Patients with Stage III, IV, or those at a high risk of recurrence.
• Participants must have a life expectancy of at least 3 months and a good performance status (ECOG 0-2).
• Study Procedures
• Specimen Collection: Researchers will collect tumor tissue through biopsy or surgery. To preserve the integrity of proteins, these samples must be snap-frozen (Fresh-Frozen) immediately after extraction.
• Analysis: The study will analyze the tissue and blood samples to characterize the patient's unique proteogenomic profile.
• Treatment Assignment: If a specific molecular variant is identified (such as HRD or ALK/ROS1/MET signatures), and a matching sub-protocol is available, the patient may be enrolled in a targeted therapy trial. Patients who do not meet these criteria will continue with the standard of care.
• Expectations and Logistics This is a multicenter, prospective screening study involving a nationwide logistics system to ensure high-quality sample transport. The study aims to enroll a total of 2,800 subjects (approximately 560 per year) and is expected to continue through December 31, 2028.
• Potential Benefits and Risks
• Benefits: Participants may gain access to targeted therapies based on their cancer's specific molecular profile.
• Risks: While the study does not add new invasive procedures beyond standard care, there are potential psychosocial risks related to genomic findings and the sharing of de-identified data for research purposes.

Conditions

Advanced Solid Tumors; Metastatic Solid Tumors; Locally Advanced Solid Tumors; Recurrent Solid Tumors; Proteogenomic Screening and Molecular Signaling; Basket Clinical Trial Framework; Targeted Therapy Based on HRD (Homologous Recombination Deficiency) and ALK/ROS1/MET Signatures

Keywords

Proteogenomics; Whole Exome Sequencing (WES); Tandem Mass Tag (TMT) labeling; Molecular Profiling; Master Protocol; Basket Trial; Precision Medicine; Multicenter Screening Study; Advanced Solid Tumors; Homologous Recombination Deficiency (HRD; ALK / ROS1 / MET; Targeted Therapy; Fresh-Frozen (FF) Specimens; Cold Ischemia Time (CIT); Nationwide Logistics System

Outcome Measures

Primary Outcomes (1)

• Rate of Successful Identification of Actionable Therapeutic Targets

  The percentage of subjects whose proteogenomic profiles-characterized through integrated Whole Exome Sequencing (WES) and phosphoproteomic analysis of fresh-frozen (FF) specimens-allow for the identification of actionable therapeutic targets for enrollment in specific basket trial sub-protocols (e.g., HRD or ALK/ROS1/MET)

  From the date of pre-treatment tissue sample collection until the completion of proteogenomic analysis and report generation, assessed up to 3 weeks (21 days) per participant.

Secondary Outcomes (3)

• Logistical Success Rate of Fresh-Frozen (FF) Specimen Transport

  From the time of tissue collection at participating hospitals until receipt and quality control verification at the central biobank, assessed up to 14 days per specimen.

• Progression-Free Survival (PFS) and Overall Survival (OS)

  From enrollment until disease progression or death from any cause, whichever occurs first, assessed up to 5 years.

• Frequency and Distribution of Molecular Signature

  From enrollment through completion of molecular signature profiling for all participants, assessed up to 36 months.

Study Arms (3)

HRD-Positive Targeted Therapy Arm

EXPERIMENTAL

HRD-targeted therapy (for Homologous Recombination Deficiency-positive signatures) (Nesuparib, Cisplatin)

Drug: Homologous Recombination Deficiency (HRD)

ALK/ROS1/MET Targeted Therapy Arm

EXPERIMENTAL

ubjects with specific ALK, ROS1, or MET gene variants or protein overexpression identified through proteogenomic analysis

Drug: ALK/ROS1/MET

Standard Care Arm

OTHER

Routine oncological treatments administered according to institutional guidelines for patients whose proteogenomic profile does not match a specific study sub-protocol

Drug: standard care treatment

Interventions

Homologous Recombination Deficiency (HRD) DRUG

This arm consists of subjects identified with Homologous Recombination Deficiency (HRD)-positive proteogenomic signatures through the master screening protocol . These subjects are eligible for matching targeted therapy sub-protocols

HRD-Positive Targeted Therapy Arm

ALK/ROS1/MET DRUG

ALK/ROS1/MET-targeted therapy (Crizotinib 250mg )

ALK/ROS1/MET Targeted Therapy Arm

standard care treatment DRUG

This arm is for subjects who do not meet the specific molecular criteria for the available targeted sub-protocols following proteogenomic screening . These subjects will continue to receive the standard-of-care treatment at their respective institutions

Standard Care Arm

Eligibility Criteria

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

You may qualify if:

• Subject has voluntarily provided written informed consent.
• Subject is 19 years of age or older.
• Histologically or cytologically confirmed metastatic or locally advanced solid tumor.
• Stage III or higher, Stage IV, or patients determined by the investigator to have a high risk of future recurrence.
• Life expectancy of ≥ 3 months.
• ECOG Performance Status of 0-2.

You may not qualify if:

• Serious or unstable pre-existing medical or psychiatric conditions that, in the investigator's judgment, could compromise subject safety during the master protocol or subsequent basket trials.
• Cognitive impairment or a diagnosis of dementia that may impede the subject's ability to participate safely.
• Inability to obtain sufficient tumor specimens for required proteogenomic analysis.
• Refusal to consent specifically to the proteogenomic testing component of the study.

Sponsors & Collaborators

• National Cancer Center, Korea: lead

Study Sites (2)

National Cancer Center, Korea

Goyang, Gyeonggido, 10408, South Korea

Location

National Cancer Center, Korea

Goyang-si, Gyeonggido, 10408, South Korea

Location

Related Publications (5)

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  PMID: 35939768 RESULT

• Zhang H, Liu T, Zhang Z, Payne SH, Zhang B, McDermott JE, Zhou JY, Petyuk VA, Chen L, Ray D, Sun S, Yang F, Chen L, Wang J, Shah P, Cha SW, Aiyetan P, Woo S, Tian Y, Gritsenko MA, Clauss TR, Choi C, Monroe ME, Thomas S, Nie S, Wu C, Moore RJ, Yu KH, Tabb DL, Fenyo D, Bafna V, Wang Y, Rodriguez H, Boja ES, Hiltke T, Rivers RC, Sokoll L, Zhu H, Shih IM, Cope L, Pandey A, Zhang B, Snyder MP, Levine DA, Smith RD, Chan DW, Rodland KD; CPTAC Investigators. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer. Cell. 2016 Jul 28;166(3):755-765. doi: 10.1016/j.cell.2016.05.069. Epub 2016 Jun 29.

  PMID: 27372738 RESULT

• Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, Wang X, Qiao JW, Cao S, Petralia F, Kawaler E, Mundt F, Krug K, Tu Z, Lei JT, Gatza ML, Wilkerson M, Perou CM, Yellapantula V, Huang KL, Lin C, McLellan MD, Yan P, Davies SR, Townsend RR, Skates SJ, Wang J, Zhang B, Kinsinger CR, Mesri M, Rodriguez H, Ding L, Paulovich AG, Fenyo D, Ellis MJ, Carr SA; NCI CPTAC. Proteogenomics connects somatic mutations to signalling in breast cancer. Nature. 2016 Jun 2;534(7605):55-62. doi: 10.1038/nature18003. Epub 2016 May 25.

  PMID: 27251275 RESULT

• Savage SR, Yi X, Lei JT, Wen B, Zhao H, Liao Y, Jaehnig EJ, Somes LK, Shafer PW, Lee TD, Fu Z, Dou Y, Shi Z, Gao D, Hoyos V, Gao Q, Zhang B. Pan-cancer proteogenomics expands the landscape of therapeutic targets. Cell. 2024 Aug 8;187(16):4389-4407.e15. doi: 10.1016/j.cell.2024.05.039. Epub 2024 Jun 24.

  PMID: 38917788 RESULT

• Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, Chambers MC, Zimmerman LJ, Shaddox KF, Kim S, Davies SR, Wang S, Wang P, Kinsinger CR, Rivers RC, Rodriguez H, Townsend RR, Ellis MJ, Carr SA, Tabb DL, Coffey RJ, Slebos RJ, Liebler DC; NCI CPTAC. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014 Sep 18;513(7518):382-7. doi: 10.1038/nature13438. Epub 2014 Jul 20.

  PMID: 25043054 RESULT

MeSH Terms

Conditions

Kenny-Caffey syndrome, Type 1

Study Officials

• Young-Woo Kim

  National Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D

Study Record Dates

• First Submitted: October 7, 2026
• First Posted: October 23, 2026
• Study Start: November 18, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share

Locations

KR (2)