Feasibility Study for Repurposing RET Inhibitors

Inclusion Criteria:

* Histologically confirmed and documented locally advanced or metastatic NSCLC, pancreatic ductal adenocarcinoma, or colorectal cancer
* Patient is currently receiving platinum-based therapy for cancer treatment
* Patients on stable EPI
* Written informed consent signed and dated by the patient prior to the performance of any study-specific procedures, sampling, or analyses
* At least 18 years-of-age at the time of signature of the informed consent form (ICF)
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
* Plasma GDF-15 level is at least 1500pg/mL
* Life expectancy exceeds 4 months, as judged by investigator
* Cachexia, defined as weight loss of \>5% body weight in the past 6 months, OR weight loss of \>2% body weight in the past 6 months with BMI \< 20

Exclusion Criteria:

* ECOG Performance Score of 3 or 4
* Is pregnant or plans to become pregnant during study duration (if patient is of childbearing potential) or plans to make someone pregnant during study duration.
* Patient has not experienced significant weight loss (defined as loss of \>5% body weight in the past 6 months, OR loss of \>2% body weight in the past 6 months with BMI \< 20)†
* Out-of-range laboratory values defined as:

  * Absolute neutrophil count (ANC) \<1.5 x 109/L
  * Hemoglobin (Hgb)90 g/L or \<9 g/dL
  * Platelets \<100 x 109/L
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases
  * Total bilirubin \>1.5 x ULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin)
  * Creatinine \>1.5 times ULN (patients may enter if creatinine is \>1.5 x ULN and estimated glomerular filtration rate (eGFR) is \>30 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration equation); confirmation of eGFR is only required when creatinine is \>1.5 X ULN
  * International Normalization Ratio (INR) \>2
* Ongoing treatment with anti-seizure medications that induce the CYP3A enzyme
* Presence of active gastrointestinal disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of selpercatinib(e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2)
* As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
* Presence of other active invasive cancers other than the ones treated in this study within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.
* Pneumonitis or QTc prolongation.