A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer

This is an interventional treatment trial for Advanced Cancer Read More

Inclusion Criteria:

• Participants must have histological or cytological confirmed diagnosis of the following tumor types that is advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate participant for experimental therapy

  • Part A: Any type of solid tumor ("all comer")
  • Part B1: Gastric or Gastroesophageal Junction (GEJ) adenocarcinoma
  • Part B2: Hepatocellular cancer (excluding fibrolamellar carcinoma)
  • Part B3: Renal cell carcinoma (any histology)
  • Part B4: Non-small cell lung cancer (squamous or non-squamous)
• Have at least 1 measurable lesion outside of the central nervous system (CNS) whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Availability of a tumor sample taken after progression on the most recent line of systemic tumor therapy or willing to undergo a tumor biopsy pre-study treatment.
• Have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale in Part A and ≤ 1 on the ECOG scale in Part B.
• Have adequate organ function.
• Routine urinalysis showing ≤1+ protein or protein/creatinine ratio <0.5. For proteinuria ≥2+ or urine protein/creatinine ratio ≥0.5, 24-hour urine must be collected and the level must be <1 gram of protein in 24 hours for subject enrollment.
• Have discontinued all previous cancer therapies and any agents that have not received regulatory approval for any indication, for at least 21 days or 5 halflives prior to study enrollment, whichever is shorter, and recovered from the acute effects for therapy.
• Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete 8 weeks (2 cycles) of treatment.
• Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for at least 3 months following the last dose of study drug. Females with childbearing potential must have had a negative serum pregnancy test 7 days before the first dose of study drug and must not be breast-feeding.

Exclusion Criteria:

• Have serious pre-existing medical conditions (at the discretion of the investigator, such as severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation).
• Have a history of hypertensive crisis or hypertensive encephalopathy or current poorly controlled hypertension despite standard medical management.
• Participant has experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, within 6 months prior to receiving study drugs.
• Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolic event during the 3 months prior to receiving study drugs.
• Are receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents. Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that they are on low-molecular weight heparin or oral factor Xa inhibitors.
• The participant is receiving chronic therapy with nonsteroidal anti-inflammatory drugs or other antiplatelet agents. Aspirin use at doses up to 325 mg/day is permitted.
• Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to receiving study drugs.
• Have a history of GI perforation and/or fistulae within 6 months prior to receiving study drugs.
• Have congestive heart failure (CHF) New York Heart Association class ≥3 or symptomatic or poorly controlled cardiac arrhythmia.
• Have undergone major surgery within 28 days prior to receiving study drugs.
• Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to receiving study drugs.
• Have a known active fungal, bacterial, and/or known viral infection. Hepatocellular cancer participants with chronic viral (B or C) hepatitis are eligible if they retain adequate liver function.
• Have liver cirrhosis with a Child-Pugh Stage of B or C.
• Have symptomatic CNS malignancy (with the exception of medulloblastoma) or metastasis.
• Have corrected QT (QTc) interval of >470 milliseconds on screening electrocardiogram (ECG).
• Have received previous treatment with ramucirumab or Emibetuzumab, except for participants enrolled in cohort B1 (Gastric or GEJ adenocarcinoma) and B4 (non- small cell lung cancer) who may have received previous ramucirumab treatment.
• Known hypersensitivity to any of the treatment components of ramucirumab or Emibetuzumab.
• Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
• Are pregnant or breastfeeding.

• For Part B4 (non-small cell lung cancer) only:

  • The participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer
  • Participants with a history of gross hemoptysis within 2 months prior to study treatment
  • The participant has radiographic evidence of intratumor cavitation, regardless of tumor histology