Patient case: 61-year-old male with Ampullary carcinoma. Genetic variant: KRAS. Other conditions: None.

Clinical trial: Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies

Summary: This is the first study to test Sym015 in humans. The primary purpose of this study is to see if Sym015 is safe and effective for patients with advanced solid tumors who do not have other available treatment options.

Detailed description: In the first part of the study (Part 1, dose-escalation), Sym015 will be evaluated for safety and tolerability. Additionally, the recommended phase 2 dose (RP2D) will be determined. Sym015 will be given at different dose levels on an every second week (Q2W) dosing schedule. Each patient will be given one fixed dose level.
  In the second part of the study (Part 2, dose-expansion), two "Basket Cohorts" will be tested to see if Sym015 is effective in patients with solid tumors with a specific genetic abnormality called MET-amplification:
  -  Q2W Basket Cohort: Sym015 at the RP2D on a Q2W dosing schedule.
  -  Q3W Basket Cohort: Sym015 at the highest safe dose tested in Part 1 on an every third week (Q3W) dosing schedule.

Eligibility: Inclusion Criteria:
  Main inclusion criteria all patients, Part 1 and Part 2:
  -  Male or female, at least 18 years of age at the time of informed consent
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  -  Life expectancy >3 months assessed during Screening
  -  Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available
  -  Tumor documented to be KRAS WT by local assessment (i.e. the tumor must express the KRAS WT, exon 2, 3 and 4)
  Additional main inclusion criteria applicable to Part 2, Basket Cohort patients ONLY:
  -  Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1)
  -  Confirmed MET-amplification
  Exclusion Criteria:
  Main exclusion criteria all patients, Part 1 and Part 2:
  -  Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1
  -  Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1 with specified allowed exceptions
  -  Use of hematopoietic growth factors within 2 weeks prior to C1/D1
  -  Active second malignancy or history of another malignancy within the last 3 years, with specified allowed exceptions
  -  Central nervous system (CNS) malignancy including primary malignancies of the CNS, known CNS or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required
  -  Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
  -  Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
  -  Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable
  -  Active uncontrolled bleeding or a known bleeding diathesis
  -  Significant cardiovascular disease or condition
  -  Abnormal hematologic, renal or hepatic function
  -  Any of the following within 2 weeks prior to C1/D1:
  -  Any serious or uncontrolled infection
  -  Any infection requiring parenteral antibiotics
  -  Unexplained fever >38.0 °C

Relevance to patient case: not relevant