Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

Tianjin Medical University Second Hospital

Status and phase: Enrolling; Phase 2

Conditions: Solid Tumor; Precision Medicine

Treatments: Drug: Palbociclib Pill; Drug: Chidamide; Drug: Pazopanib Pill; Drug: Vebreltinib Enteric Capsules; Drug: Dabrafenib; Drug: Anlotinib; Drug: Temozolomide capsule; Drug: PD-1/PD-L1/PD-1&CTLA4 inhibitor; Drug: Target Gene; Drug: Lenvatinib Capsules; Drug: Sacituzumab Govitecan-Hziy 180 MG; Drug: Alpelisib Pill; Drug: Trametinib tablet; Drug: Olaparib tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT06739395

MyCustom-02

Details and patient eligibility

About

The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.

Full description

Using comprehensive genome sequencing to analyze recurrent and metastatic solid tumors that have failed previous conventional treatments, and matching possible targeted therapy drugs to screen for potential effective treatment drugs until tumor disease progression, and then continuing to monitor tumor resistance mutation signals and provide matching therapy, can help improve the clinical outcomes of patients with advanced refractory tumors, and is also an important direction for personalized and precise treatment of tumors in the future. Therefore, the investigators designed this study to explore the feasibility, effectiveness, and safety of targeted therapy based on tumor molecular feature matching for advanced solid tumor patients who have failed previous treatments. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including clinical efficacy ,clinical safety and exploratory endpoints such as biomarkers for drug response, change in the tumor microenvironment. The core concepts of the clinical research interventional initiated include: target priority principle, combination therapy principle, individualized dose adjustment method for combination therapy, and Bayesian adaptive trial design. For some clinical studies, to meet the primary objective, at least 35% of participants had to achieve a PFS2(Progression-Free Survival 2)/PFS1(Progression-Free Survival 1) ≥ 1.3 in a sample population of 25 evaluable patients. Sample size was calculated using an exact single-stage design for phase II studies with a one-sided type I error of 5% and a power of 90% under the assumption that PFS2/PFS1≥ 1.3 in ≤10% of patients would be clinically irrelevant, while a success rate ≥ 35% would merit further investigation.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Recurrent or metastatic malignant solid tumors diagnosed by histology or cytology;
2. ECOG score 0-4 (3-4 points only for patients with tumor burden);
3. Those who fail or cannot tolerate standard treatment, or those who refuse standard treatment;
4. At least one measurable lesion that meets the RECIST 1.1 standard;
5. Expected survival period ≥ 3 months;
6. Age ≥ 18 years old;
7. Tumor tissue blocks with sufficient formalin fixed paraffin embedding (FFPE), or chest or ascites with cancer cells detected during treatment (not less than 200ml), or excised metastatic lymph nodes, or peripheral blood (approximately 5m1) can be used for genetic testing;
8. Understand and voluntarily participate in this study, and sign the informed consent form.

Exclusion criteria

1. Patients who have actively undergone or are currently participating in clinical trials for treatment;
2. Serious or uncontrolled medical diseases (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental diseases/social conditions that limit the compliance with the research requirements) that the researchers think will confuse the research treatment response analysis;
3. Pregnant or lactating patients, or any patients with fertility, have not taken appropriate pregnancy prevention measures.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 9 patient groups

Monotherapy

Other group

Description:

In the OncoKB(Precision Oncology Knowledge Base) database, the gene alteration has a variant of clinical evidence in this tumor or other tumor types and is considered to be an interventional variant. Cohort-1may include different observation subgroups（dMMR/MSI-H,TMB-H,NTRK fusion,RET-fusion,BRAF(p.V600E),KRAS(p.G12C),HER2(IHC,3+)）. For example, substudy-1: monotherapy/combination therapy for patients with A1-relative. Substudy-x: monotherapy/combination therapy for patients with Ax-relative.

Treatment:

Drug: Target Gene

Combination therapy-cohort1

Experimental group

Description:

The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration).

Treatment:

Drug: Trametinib tablet

Drug: Olaparib tablet

Drug: Sacituzumab Govitecan-Hziy 180 MG

Drug: Alpelisib Pill

Drug: Lenvatinib Capsules

Drug: Target Gene

Drug: PD-1/PD-L1/PD-1&CTLA4 inhibitor

Drug: Temozolomide capsule

Drug: Dabrafenib

Drug: Anlotinib

Drug: Vebreltinib Enteric Capsules

Drug: Chidamide

Drug: Pazopanib Pill

Drug: Palbociclib Pill

Combination therapy-cohort2

Experimental group

Description:

The characteristics of enrolled patients are primary or secondary drug resistance during treatment.

Treatment:

Drug: Trametinib tablet

Drug: Olaparib tablet

Drug: Sacituzumab Govitecan-Hziy 180 MG

Drug: Alpelisib Pill

Drug: Lenvatinib Capsules

Drug: Target Gene

Drug: PD-1/PD-L1/PD-1&CTLA4 inhibitor

Drug: Temozolomide capsule

Drug: Dabrafenib

Drug: Anlotinib

Drug: Vebreltinib Enteric Capsules

Drug: Chidamide

Drug: Pazopanib Pill

Drug: Palbociclib Pill

Olaparib+Anlotinib/Temozolomide

Experimental group

Description:

The gene TP53 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.

Treatment:

Drug: Olaparib tablet

Drug: Temozolomide capsule

Drug: Anlotinib

Trametinib±Vebreltinib

Experimental group

Description:

The gene MAP2K1 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.

Treatment:

Drug: Trametinib tablet

Drug: Dabrafenib

Alpelisib

Experimental group

Description:

The PMA(PI3K/mTOR/AKT ) pathway active alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.This subgroup is not included in breast cancer patients.

Treatment:

Drug: Alpelisib Pill

Palbociclib+Pazopanib

Experimental group

Description:

The gene alteration(Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19)) that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.

Treatment:

Drug: Pazopanib Pill

Drug: Palbociclib Pill

Vebreltinib

Experimental group

Description:

MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping/MET-amplification.

Treatment:

Drug: Vebreltinib Enteric Capsules

Combination therapy group based on PD-1/L1 immune checkpoint inhibitors

Experimental group

Description:

MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy.

Treatment:

Drug: Lenvatinib Capsules

Drug: Target Gene

Drug: PD-1/PD-L1/PD-1&CTLA4 inhibitor

Drug: Chidamide