A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer

Study Overview
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Brief Summary
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The purpose of this study in participants with advanced cancer is to learn more about the safety of ramucirumab when given by injection under the skin (subcutaneous injection). The study will also measure how much ramucirumab gets into the bloodstream and how long it takes the body to get rid of it.

Official Title
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A Phase 1, Nonrandomized, Open-Label Investigation of Subcutaneous Ramucirumab Administration in Participants With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Ramucirumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). In the judgment of the investigator, be an appropriate candidate for experimental therapy and: For Cohort A only: Have exhausted all anticancer treatments with proven clinical benefit OR For Cohorts B and C only: Must have one of the three conditions below: Have exhausted all anti-cancer treatments with proven clinical benefit, OR Have hepatocellular carcinoma or gastric cancer who have received prior treatment, and where IV ramucirumab monotherapy is clinically acceptable treatment after progression OR Have a diagnosis for which IV ramucirumab in combination with additional anticancer therapy is clinically acceptable treatment Additionally, it must be clinically acceptable to delay initiation of the combination partner for 3 weeks from the initiation of ramucirumab dosing. Eastern Cooperative Oncology Group performance status score of 0 or 1. Have discontinued all previous treatments for cancer with adequate wash-out period and recovered from the acute effects of therapy. Have adequate hematologic, hepatic, and renal functions and electrolytes. Males and females of child-bearing potential must agree to use highly effective contraceptive methods during study treatment and for at least 84 days/12 weeks following the last dose of study drug. Exclusion Criteria: Have uncontrolled hypertension defined as systolic blood pressure (BP) >150 mmHg or diastolic BP >90 mmHg despite standard medical management. Have significant bleeding disorders or experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment. Have hepatic impairment (such as severe liver cirrhosis Child-Pugh B [or worse], cirrhosis with a history of hepatic encephalopathy, clinically meaningful ascites requiring ongoing treatment with diuretics and/or paracentesis, or history of hepatorenal syndrome). Have experienced any arterial thromboembolic events (ATEs), including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, ≤6 months prior to randomization. The participant has clinically relevant congestive heart failure (CHF; New York Heart Association [NYHA] Grade ≥2) or symptomatic or poorly controlled cardiac arrhythmia. Have symptomatic central nervous system (CNS) metastases. Screening is not required. Have history of GI perforation and/or fistula within 6 months prior to enrollment. Have an active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness. Have a serious or non-healing wound, ulcer, or bone fracture within 4 weeks prior to enrollment. Have received IV ramucirumab in the past.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab<br>Participants received starting dose of 700 milligram (mg) ramucirumab loading dose (LD) subcutaneously (SC) followed, a week later, by 350 mg ramucirumab maintenance dose (MD) administered SC once a week. | Drug: Ramucirumab<br>* Administered SC<br>* Other names: LY3009806;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab | PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days. | Cycle (C) 1 Day (D) 1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose | 
| PK: Maximum Concentration (Cmax) of Ramucirumab | PK: Cmax of Ramucirumab was evaluated. | C1D1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose | 
| PK: Serum Trough Concentration (Ctrough) of Ramucirumab | Ctrough of Ramucirumab was evaluated. | C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Anti-Ramucirumab Antibodies | Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted). | C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose | 
| Number of Participants With Injection Site Reactions (ISRs) | The number of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Cycle 1, Cycle 2, Cycle 3: D1, D8, D15, D22: 5-15 min, 60 min post injection; C1D2: 24 hours (h) post injection; C1D4 (± 1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety