araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation

Summary: Rationale:
  Advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 11 months when treated with gefitinib. Combination of gefitinib and berberine could improve efficacy in lung cancer with EGFR mutation in vivo and vitro. The investigators hypothesize that progression-free survival could be improved by combination of gefitinib and berberine.

Detailed description: Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP-1) were found in gefitinib-resistance NSCLC cells. Berberine, an effective suppressor of SREBP1 and lipogenesis regulated through ROS/AMPK pathway, selectively inhibited the growth of gefitinib-resistance NSCLC cells but not that of normal cells. It effectively caused mitochondrial dysfunction, activated reactive oxygen species (ROS)/AMPK pathway and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor and palmitic acid significantly reduced the effect of Berberine. In in vivo study, treatment of Berberine led to significant inhibition of mouse tumor xenograft growth.

Eligibility: Inclusion Criteria:
  -  Age ≥ 18 years
  -  ECOG performance status 0-2
  -  Adequate haematological function, coagulation, liver function and renal function
  -  Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC)
  -  TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease)
  -  Measurable or evaluable disease (according to RECIST 1.1 criteria).
  -  Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)
  Exclusion Criteria:
  -  Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma.
  Patients with any known significant ophthalmologic anomaly of the ocular surface
  -  Patients who received prior chemotherapy for metastatic disease
  -  Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF
  -  Pregnancy

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Lung Cancer Next Generation Sequencing Using the Oncomine Comprehensive Assay

Summary: Currently, publicly funded standard of care testing in Ontario for stage IV lung cancer patients uses individual gene tests to look for mutations in the EGFR and ALK genes. This testing broadens treatment options for patients, however there are other gene mutations with corresponding targeted treatments that are not routinely tested for. This study will evaluate the utility and added value of using a next generation sequencing (NGS) panel, the Oncomine Comprehensive Assay v3, to profile stage IV lung cancer patients.


Eligibility: Inclusion Criteria:
  -  Age ≥ 18 years of age
  -  Pathologic or cytologic confirmation of lung adenocarcinoma (mixed adenocarcinoma and sarcomatoid features permitted)
  -  Stage IV disease
  -  Sufficient FFPE tumour tissue for OCCP testing
  -  Performance status 0-2
  -  Candidates for targeted therapy (TKIs) and/or clinical trials as determined by the patient's medical oncologist
  -  Prognosis > 6 months
  -  Known translocations of RET, MET exon14 skipping variants, or MET amplification are allowed
  Exclusion Criteria:
  ● Patients with known EGFR, KRAS, BRAF and ERBB2 mutations or ALK or ROS1 fusions at study entry unless acquired resistance to molecularly targeted therapy

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: A Phase 1, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation.

Summary: Evaluate the safety and tolerability of AMG 510 in adult subjects with KRAS p.G12C mutant solid tumors.
  Estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups.


Eligibility: Inclusion Criteria:
  -  Men or women greater than or equal to 18 years old.
  -  Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through DNA sequencing.
  -  Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
  Exclusion Criteria:
  -  Active brain metastases from non-brain tumors.
  -- History or presence of hematological malignancies unless curatively treated with no evidence of disease
  -  Myocardial infarction within 6 months of study day 1.
  -  Symptomatic congestive heart failure (New York Heart Association greater than class II)
  -  Unstable angina
  -  Cardiac arrhythmia requiring medication
  -  Gastrointestinal (GI) tract disease causing the inability to take oral medication.
  -  Active infection requiring intravenous (IV) antibiotics within 1 weeks of study enrollment (day 1)
  -  Positive Hepatitis B Surface Antigen (HepBsAg) or positive Hepatitis total core antibody with negative HepBsAg
  -  Detectable Hepatitis C virus
  -  Known positive test for HIV
  -  Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible [defined as having been present and stable for greater than 6 months] may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor)

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Study for Patients With Lung Metastatic Advanced Gastric Cancer and NSCLC Treated With Apatinib

Summary: The primary end point was progression-free survival (PFS), secondary end points included duration of locoregional control (LRC), overall survival (OS), quality of life and safety. For metastatic lung cancer, LRC is the local control of metastatic lung tumor here.

Detailed description: Between February 1, 2015 and May 19, 2018, 433 adult patients with gastric adenocarcinoma, lung adenocarcinoma and lung squamous cell carcinoma, multiline chemotherapy failure and lack of standard treatment, received oral apatinib 250 mg daily at the Affiliated Hospital of Qingdao University. Histologically proven were identified retrospectively using the Clinical Research Information Systems (CRIS) database. All patients were with Karnofsky performance status ≥70% or an Eastern Cooperative Oncology Group performance status of 0 to 1, with stable hepatic, hematologic, and renal functions. Cardiac disease and hemorrhagic disease were excluded. All patients had pre-therapy chest computed tomography (CT) prior to apatinib treatment, and follow-up chest CT at least every 4 weeks. The primary end point was progression-free survival (PFS), secondary end points included duration of locoregional control (LRC), overall survival (OS), quality of life and safety. For metastatic lung cancer, LRC is the local control of metastatic lung tumor here. Other patient demographic and clinical data, including age, gender; stage of disease, apatinib administered inclusion and withdrawal date, adverse events, oncologic clinical response, comorbid conditions, and smoking history, were retrieved from the CRIS database.

Eligibility: Inclusion Criteria:
  1. Between February 1, 2015 and May 19, 2018, 433 adult patients with gastric adenocarcinoma, lung adenocarcinoma and lung squamous cell carcinoma
  2. Multiline chemotherapy failure and lack of standard treatment, received oral apatinib 250 mg daily at the Affiliated Hospital of Qingdao University.
  3. Histologically proven were identified retrospectively using the Clinical Research Information Systems (CRIS) database.
  4. All patients were with Karnofsky performance status over 70% or an Eastern Cooperative Oncology Group performance status of 0 to 1, with stable hepatic, hematologic, and renal functions.
  Exclusion Criteria:
  1. Cardiac disease and hemorrhagic disease were excluded.
  2. Patients with lung cavitation before apatinib treated.

Relevance to patient case: not relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Detailed description: This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Eligibility: Inclusion Criteria:
  -  Participant (male or female) ≥18 years of age
  -  Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  -  Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: RTK mutations, amplifications or rearrangements, KRASG12, BRAF Class 3, or NF1 LOF mutations
  -  Adequate hematologic, hepatic and renal function
  -  Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
  -  Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
  Exclusion Criteria:
  -  Known or suspected leptomeningeal or brain metastases or spinal cord compression
  -  Primary central nervous system (CNS) tumors
  -  Clinically significant cardiac disease
  -  Active, clinically significant interstitial lung disease or pneumonitis
  -  History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
  -  Known HIV infection
  -  Active/chronic hepatitis B or C infection
  -  Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
  -  Females who are pregnant or breastfeeding

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Investigation of the Contents and Prognostic Values of Glucose Metabolism Molecules in Patients With Lung Adenocarcinoma

Summary: Detect the contents of glucose metabolism molecules in the tumor and adjacent normal samples of about 100 patients with lung adenocarcinoma using mass spectroscopy. Analyze the correlation between the contents and the clinicopathological characteristics and survival.


Eligibility: Inclusion Criteria:
  -  Primary lung adenocarcinoma
  Exclusion Criteria:
  -  Other tumor histories, received radiotherapy or chemotherapy before surgery, tumor or adjacent normal tissues can't be obtained, patient rejected.

Relevance to patient case: not relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer

Summary: this study is to analyze the survival condition of different groups about non-small cell lung cancer patients with KRAS mutations。The groups are made according to the treatment regime,brain metastases and gene mutation


Eligibility: Inclusion Criteria:
  -  advanced non-small cell lung cancer stage IIIB/IV
  -  KRAS mutation
  -  non-squmous
  Exclusion Criteria:
  -  squmous non-small cell lung cancer

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)

Summary: The purpose of this study is to determine whether nivolumab plus ipilimumab or nivolumab alone is effective and safe in the treatment of solid tumors with High Tumor Mutational Burden (TMB-H)


Eligibility: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with TMB-H who are refractory to standard local therapies, or for which no standard treatment is available.
  -  Available tumor tissue and blood for TMB testing
  -  Participants must have measurable disease for response assessment
  Exclusion Criteria:
  -  Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease
  -  Participants who received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  -  Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment
  Other protocol defined inclusion/exclusion criteria could apply

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Effect of Chemotherapy on TMB in NSCLC

Summary: Tumor mutation burden is identified as an important biomarkers for predicting PD-1/PD-L1 inhibitors in advanced Non-Small Cell Lung Cancer. Several previous clinical trials have demonstrated that chemotherapy could enhance the efficacy of PD-1/L1 immunotherapy in NSCLC such as Checkmate-227, Impower-150, Keynote-189, etc. Pre-clincial experiment shows that chemotherapy could increase CD8 TIL infiltration in tumor microenvironment, activate T cell immune reaction. However, it remains unclear whether chemotherapy could affect tumor mutation burden in advanced NSCLC patients. The present study aims to evaluate whether tumor mutation burden will change after receiving chemotherapy in advanced NSCLC patients.


Eligibility: Inclusion Criteria:
  -  Advanced NSCLC diagnosed histologically; Expected survival ≥ 6 month;
  -  Without Druggable molecular events (EGFR, ALK, c-Met, BRAF, Ret, etc)
  -  ECOG / PS score: 0-2, and the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min
  Exclusion Criteria:
  -  Patient can not comply with research program requirements or follow-up;
  -  Patient will receive immunotherapy;

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Metastatic Colorectal Cancer Treated With Regorafenib and FOLFIRI

Summary: The survey is a retrospective study to evaluate the prognotic value of EGFR expression, KRAS mutations and tumor sideness in patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.

Detailed description: Primary objective:
  Progression-free survival
  Secondary objecive:
  Overall survival, best objective response, disease control rate and adverse events
  Number of Subjects: 41 patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.
  Plan of the Study:
  1. This is a retrospective study.
  2. Study Schedule Study date: the time getting approval letter issued by both regulatory authority and institutional review board (IRB). Duration of the study: 5 years.
  3. Duration of Treatment: Treatment was administered until disease progressed.

Eligibility: Inclusion Criteria:
  -  Age between 20-85 years old
  -  Histologically proven metastatic colorectal cancer (mCRC).
  -  Patients with progressing mCRC who were previously treated with FOLFOX, FOLFIRI, anti-VGFR monoclonal antibody (MoAb), and anti-EGFR MoAb if KRAS-wild-type tumors were identified.
  -  Patient was able to understand the requirements of the study and written informed consent was obtained from each subject.
  Exclusion Criteria:
  -  Patients who do not meet the including criteria or unwilling to participate

Relevance to patient case: not relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer

Summary: This is a randomized, open-label, multi-center, phase II trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus Pemetrexed and Carboplatin in Subjects with KRAS mutant stage IV non-squamous Non-small Cell Lung Cancer


Eligibility: Inclusion Criteria:
  1. Subjects with histopathological diagnosis of adenocarcinoma non-small cell lung cancer (NSCLC) and clinical stage IV
  2. has not received prior systemic treatment for metastatic NSCLC.
  3. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
  4. confirmes by the central laboratory as KRAS gene mutation
  5. Has archived Tumor tissue samples
  6. Subject must have a measurable target lesion based on RECIST v1.1 .
  7. Women of childbearing age must undergo a serological pregnancy test within 3 days before the first dose with negative results. Female subjects of reproductive age and male subjects whose spouse is a woman of reproductive age must agree to effective contraception within 180 days after the study period and the last dose of the study drug.
  8. Subjects should be voluntarily participate in clinical studies and informed consent should be signed.
  Exclusion Criteria:
  1. active brain metastases and meningeal metastasis
  2. uncontrollable tumor-related pain
  3. massive pleural effusion, peritoneal effusion or pericardial effusion which cannot be controlled by repeated drainage;
  4. radiotherapy to lung that is >30 Gy within 24 weeks before the first dose,
  5. imaging (CT or MRI) showed that the tumor invading the large vessels
  6. Known EGFR/ALK mutation.
  7. subjects with any known or suspected autoimmune diseases
  8. subjects with known or suspected interstitial pneumonia;
  9. Subjects with severe cardiovascular and cerebrovascular diseases
  10. arteriovenous thrombosis events, such as deep vein thrombosis and pulmonary embolism, occurred within 3 months;
  11. female subjects who are pregnant or lactation or who plan to be pregnant during the study period;
  12. positive HIV test;
  13. active hepatitis B
  14. evidence of active TB infection within 1 year before first dose;
  15. severe infection occurred within 4 weeks before the first dose
  16. patients with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month
  17. subjects who is on systemic immunogenic agents;
  18. a history of severe allergic reactions to other monoclonal antibodies/fusion proteins;
  19. History of severe allergic reactions to carboplatin or pemetrexed or their preventive drugs;

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

Clinical trial: MRTX849 in Patients With Cancer Having a KRAS G12C Mutation

Summary: Evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed description: Evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally-available small molecule inhibitor of KRAS G12C.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
  -  Unresectable or metastatic disease
  -  Standard treatment is not available or patient declines
  -  Adequate organ function
  Exclusion Criteria:
  -  Active brain metastases
  -  History of intestinal disease or major gastric surgery or inability to swallow oral medications
  -  Other active cancer

Relevance to patient case: possibly relevant