araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.

Summary: This study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation phase (I) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion phase (II) which will characterize treatment of LAG525 as a single agent and in combination with PDR001 at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  Phase I part:
  - Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
  Phase II part:
  -  Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have had disease progression following their last prior therapy and fit into one of the following groups:
  -  Group 1: NSCLC
  -  Group 2: Melanoma
  -  Group 3: Renal cancer
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  -  Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines.
  Exclusion Criteria:
  -  History of severe hypersensitivity reactions to study treatment ingredients or other mAbs
  -  Active, known or suspected autoimmune disease
  -  Active infection requiring systemic antibiotic therapy
  -  HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  -  Patients receiving chronic treatment with systemic steroid therapy, other than replacement-dose corticosteroids in the setting of adrenal insufficiency
  -  Patients receiving systemic treatment with any immunosupressive medication
  -  Use of live vaccines against infectious disease within 4 weeks of initiation of study treatment
  -  Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.
  -  Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks
  -  History of drug-induced pneumonitis or current pneumonitis.

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy

Summary: KIT is a receptor tyrosine kinase that binds to stem-cell factor (SCF), activating a series of downstream effector pathways. KIT is an established therapeutic target in cancer with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and significant benefit is achieved with various small molecule inhibitors of KIT such as imatinib mesylate. Moreover, there is increasing evidence implicating KIT mutations as tractable therapeutic targets in melanoma. Additional information is required to characterize the functional role of low-frequency mutations in KIT and to determine whether amplification of wild type KIT is a real driver that can be targeted therapeutically. Except GIST and melanoma, other solid cancers were reported to have KIT mutation even in low frequency. A molecular profiling of the tumors of patients referred to the phase I clinic at the M.D. Anderson Cancer Center showed KIT mutation in 7 patients in total of 431 patients (2%).
  Hence, the investigators planned this study to apply the molecularly targeted agent, imatinib to various types of cancers harboring KIT mutation or amplification.


Eligibility: Inclusion Criteria:
  1. age ≥ 20
  2. advanced, refractory cancer patients who failed standard of care (SOC)
  3. KIT aberration: defined as mutation in exons 9, 11, 13, 17 or 18, or nanostring CNV by quantitative PCR (greater than 3 copies) or subject with specific sensitivity (Z-score<-1) to imatinib by Avatar scan whose disease has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy
  4. ECOG performance status of 0~2
  5. measurable or evaluable lesion per RECIST 1.1 criteria
  6. adequate marrow, hepatic, renal and cardiac functions
  -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  -  Total serum bilirubin ≤ 1.5 x ULN
  -  Absolute neutrophil count(ANC) ≥ 1,500/uL
  -  Platelets ≥ 100,0000/uL
  -  Hemoglobin ≥ 9.0 g/dL
  7. provision of a signed written informed consent
  Exclusion Criteria:
  1. severe co-morbid illness and/or active infections
  2. pregnant or lactating women
  3. history of major surgery or radiotherapy within 4 weeks
  4. active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
  5. known history of hypersensitivity to study drugs

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors

Summary: This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.


Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Life expectancy at least 12 weeks
  -  Adequate hematologic and end organ function
  -  Negative pregnancy test and willingness to utilize contraception among women of childbearing potential
  -  Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
  -  Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
  -  For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer
  -  For the expansion stage, evaluable for PD-L1 expression
  -  Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled
  Exclusion Criteria:
  -  Significant cardiovascular or liver disease
  -  Major surgery within 28 days of study drug
  -  Any anti-cancer therapy within 3 weeks of study drug
  -  Malabsorption syndrome or poor upper gastrointestinal integrity
  -  Primary central nervous system (CNS) malignancy or active metastases within 5 years
  -  Uncontrolled tumor pain
  -  Autoimmune disease other than stable hypothyroidism or vitiligo
  -  Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis
  -  Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug
  -  Live attenuated vaccine within 4 weeks of study drug
  -  Known history or predisposition to QT interval prolongation
  -  Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Hepatic RFA Increases T Cell Infiltraion and PD-L1 Expression in Primary Colorecatl Cancer

Summary: It has been shown that RFA induced systemic tumor antigen-specific T cell responses in human carcinoma. However, there are insufficient studies on the immune modulation of tumor microenviroment (TME) outside of the ablation zone. In order to study how RFA modifies TME in human cancer patients, investigators performed a retrospective study of a unique cohort of patients who suffered from synchronous CRCLM.

Detailed description: Radiofrequency ablation (RFA) is widely used as a local treatment for tumors such as small hepatocellular carcinomas, renal cancer and solitary colorectal cancer liver metastases (CRCLM). RFA induces localized coagulation necrosis and leads to the release of large amounts of cellular debris in situ, which can serve as a source of tumor antigens to elicit host adaptive immune responses against tumors. Several studies on preclinical animal models have shown that localized tumor ablation by RFA can induce systemic T-cell mediated antitumor immunity. Antigen-specific T cell immune responses were also observed in patients with hepatic tumors after RFA therapy. However, the RFA-induced immune responses are not sufficient to prevent tumor recurrence. The underlying mechanisms remain obscure.
  Programmed death-ligand 1 (PD-L1), an important immune checkpoint molecule, is often up-regulated on tumor cells and tumor associated myeloid cells. It impairs T cell-mediated immune responses upon engagement with its cognate co-inhibitory receptor PD-1, which is always highly expressed on tumor-infiltrating lymphocytes. PD-L1 expression can be induced by pro-inflammatory cytokines, especially type I interferon (IFN), as an important self-limiting mechanism to prevent rampant autoimmunity. Recent studies show that PD-L1 expression on tumor cells is associated with T cell infiltration, suggesting PD-L1 is actively involved in suppressing antitumor immune responses in the tumor microenvironment (TME). Whether the PD-L1/PD1 axis is involved in modulating the antitumor T cell immune responses induced by RFA is unclear.
  The objective of this investigation was to study the RFA-induced immune responses in tumor tissues from cancer patients.

Eligibility: Inclusion Criteria:
  Patients with histologically confirmed asynchronous liver metastases received initial hepatic RFA or initial primary tumor resection.
  Exclusion Criteria:
  1. Preoperative CT, RT and other antitumor treatment
  2. Emergency surgery
  3. Initial hepatectomy
  4. No qualified endoscopic biopsy

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: A Comparative Study in Chinese Subjects With Chemotherapy Naïve Stage IV Melanoma Receiving Ipilimumab (3 mg/kg) vs. Dacarbazine

Summary: The purpose of this study is to determine whether Ipilimumab will extend the life of chinese patients with Chemotherapy Naive Stage IV Melanoma more than Dacarbazine as well as to examine safety in this patient population.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Chinese males and females ≥ 18 years of age
  -  Histologic diagnosis of malignant melanoma
  -  Chemotherapy naive Stage IV melanoma (AJCC 2010)
  -  Life expectancy of ≥ 16 weeks
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  Exclusion Criteria:
  -  Evidence of brain metastases on brain imaging
  -  Primary ocular or mucosal melanoma
  -  Any other malignancy from which the patient has been disease-free for less than 5 years
  -  BRAF status cannot be determined by Screening test
  -  Human Immunodeficiency Virus (HIV) positive or hepatitis B surface antigen (HBsAg) positive, or active Hepatitis C infection

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: myDC/pDC in Stage III Melanoma Patients

Summary: This is an interventional study to test the immunogenicity of combined adjuvant myDC and pDC vaccination versus adjuvant myDC or pDC vaccination alone in stage III melanoma patients.

Detailed description: Stage lll melanoma patients will receive pDC (arm A, n=10), myDC (arm B, n=10) or combined pDC/myDC (arm C, n=10). Subsequent vaccinations will be performed according to the protocol: 2 biweekly vaccinations of intranodal injections with pDC, myDC or the combination with pDC and myDC. After each vaccination the investigators will examine peripheral blood for proliferative and humoral KLH immune responses. After the vaccinations, a DTH with peptide loaded blood DC is performed from which biopsies are taken for T cell analysis. lf patients remain disease free, the investigators will repeat this cycle with a 6 months interval up to a total of three cycles. lf a tumor recurrence occurs a biopsy will be taken for laboratory evaluation.

Eligibility: Inclusion Criteria:
  -  stage III melanoma
  -  WHO performance status 0-1
  -  radical lymph node dissection is schedule or performed within 12 weeks prior to start of study treatment
  Exclusion Criteria:
  -  irresectable disease
  -  any concurrent adjuvant therapy
  -  concomitant use of oral immunosuppressive drugs
  -  autoimmune diseases

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers

Summary: This is a phase 1/1b open-label, multicenter, dose-selection study of CPI-444, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of CPI-444 as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various solid tumors. CPI-444 blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.

Detailed description: This is a phase 1/1b open-label, multicenter, dose-selection study of CPI-444, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of CPI-444 as a single agent and in combination with atezolizumab, an intravenous PD-L1 inhibitor. CPI-444 blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.

Eligibility: Inclusion Criteria
  1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  2. Documented incurable cancer with one of the following histologies: non-small cell lung cancer, malignant melanoma, renal cell cancer, triple negative breast cancer, colorectal cancer with microsatellite instability (MSI), and bladder cancer.
  3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  4. At least 1 but not more than 5 prior systemic therapies for advanced/recurrent or progressing disease.
  Exclusion Criteria
  1. History of severe hypersensitivity reaction to monoclonal antibodies.
  2. Any active autoimmune disease or a documented history of serious autoimmune disease within the past 5 years requiring immunosuppressive therapy.
  3. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or clinical symptoms of active pneumonitis.
  4. The use of any investigational medication or device in the 30 days prior to screening and throughout the study is prohibited.
  5. If a patient is currently receiving denosumab, this must be discontinued prior to enrollment. Substitution with biphosphonates are acceptable.

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Phase I Study of PDR001 in Patients With Advanced Malignancies.

Summary: The purpose of this study is to characterize the safety, tolerability, Pharmacokinetics (PK), and antitumor activity of PDR001 administered intravenous (i.v.) as a single agent to Japanese patients.


Eligibility: Inclusion Criteria:
  -  Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by response evaluation criteria in solid tumors (RECIST) version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
  -  ECOG Performance Status ≤ 2
  Exclusion Criteria:
  -  Active autoimmune disease
  -  Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  -  Prior PD-1- or PD-L1-directed therapy
  Other protocol defined inclusion/exclusion may apply.

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Expression of Tumor Markers in Circulating Tumor Cells of Metastatic Hormone-sensitive Prostate Cancer

Summary: As prostate cancer progresses, tumor cells dissociate and enter the bloodstream. Considered a "liquid biopsy," these circulating tumor cells (CTC) can show how a patient's cancer evolves and responds to treatments. The purpose of this study is to determine whether sequentially analyzing the expression of tumor markers in circulating tumor cells in newly diagnosed metastatic hormone-sensitive prostate cancer patients can predict the outcome of these patients.


Eligibility: Inclusion Criteria:
  1. Male patients;
  2. 18 yrs and older, and 80 yrs and younger;
  3. Histologically or cytologically proven prostate adenocarcinoma;
  4. Imaging examinations including Emission Computed Tomography (ECT),Positron Emission Tomography (PET),Computed Tomography(CT)and Magnetic Resonance Imaging (MRI) revealed non-regional lymph node metastasis, bone metastasis, or visceral metastasis;
  5. Not yet receiving hormonal therapy;
  6. Not yet receiving chemotherapy previously;
  7. Not yet receiving radical prostatectomy, radiotherapy, or transurethral resection of the prostate (TURP) previously;
  8. Patients are willing to participate and can be followed up regularly；
  Exclusion Criteria:
  1. Received radical prostatectomy, radiotherapy, or transurethral resection of the prostate (TURP) previously;
  2. Received androgen deprivation therapy (including surgical castration, medical castration, anti-androgen therapy, and maximum androgen blockade) before inclusion;
  3. Patients received chemotherapy previously;
  4. Combined with other malignant tumor history (in addition to the skin basal cell carcinoma or other tumors that have been cured more than five years);

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Study Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Summary: The main purpose of this study is to compare nivolumab and ipilimumab with the Extreme study regimen as first line treatment in patients with recurrent or metastatic squamous cell of the head and neck cancer


Eligibility: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx & larynx) that is not amenable to curative therapy.
  -  No prior systemic cancer therapy for recurrent or metastatic disease (except if chemotherapy was part of multimodal treatment completed 6 months prior to enrolment).
  -  Measurable disease detected by imaging exam (CT or MRI).
  -  Have tumor tissue for PD L1 expression testing, and for oropharyngeal cancer have results from testing of HPV p16 status.
  Exclusion Criteria:
  -  Metastatic or recurrent carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, squamous cell carcinoma originating from skin and salivary glands or non squamous histologies (eg. mucosal melanoma).
  -  No prior treatment with anti PD1, anti PD L1, anti CTLA 4 antibody or any other antibody or drugs targeting T cell costimulation or checkpoint pathways, or cetuximab or EGFR inhibitors in any treatment setting.
  -  Patients with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder.
  -  Inadequate hematologic, renal or hepatic function.
  Other protocol defined inclusion/exclusion criteria could apply

Relevance to patient case: not relevant
Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: An Investigational Study of Infliximab With Prednisone or Methylprednisolone Versus Prednisone Combination Treatment in Immune Related or Severe Diarrhea in Patients Treated With Yervoy and/or Opdivo

Summary: The purpose of this study is to compare the effects of Infliximab and oral prednisone versus methylprednisolone and oral prednisone in patients with melanoma, lung cancer, or renal cell carcinoma who have immune related Grade 3-4 diarrhea for up to 3 days or persistent Grade 2 diarrhea for more than 5 days after treatment with Yervoy and/or Opdivo


Eligibility: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Subjects must have melanoma or lung cancer or renal cell carcinoma and received ipilimumab or nivolumab as a single treatment or in combination
  -  Subject must have NCI common toxicity Grade 3-4 immune-related diarrhea for up to 3 days or persistent Grade 2 diarrhea for more than 5 days
  -  Subjects must be discontinued from ipilimumab or nivolumab as monotherapy or with the combination regimen
  Exclusion Criteria:
  -  Subjects who received other anti Cytotoxic T-lymphocytic antigen (CTLA-4) (non-ipilimumab) or other anti-Programmed death-1 (PD-1) (non-nivolumab) treatment
  -  Subjects treated with systemic Corticosteroid (CST) within 1 week before randomization and subjects treated with infliximab within 7 weeks before randomization
  -  Subjects with known history of tuberculosis
  -  Subjects with immunosuppressive disease that require use of systemic steroids or immunosuppressive treatment
  -  Subjects allergic to infliximab, inactive components of infliximab, murine proteins and methylprednisolone
  Other protocol defined inclusion/exclusion criteria could apply

Relevance to patient case: not relevant