A Study of LY3127804 With Ramucirumab in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety of the study drug known as LY3127804 given as monotherapy and in combination with Ramucirumab for participants with advanced or metastatic solid tumors. The study will also include a safety exploration for the combination of LY3127804 plus ramucirumab and paclitaxel

Official Title
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A Phase 1 Study of LY3127804 as Monotherapy and in Combination With Ramucirumab in Patients With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: LY3127804
* Drug: Ramucirumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of cancer that is advanced and/or metastatic. Have disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST ) version 1.1. Have adequate organ function. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Have discontinued previous treatments for cancer for at least 28 days or 5 half-lives prior to study enrolment. Exclusion Criteria: Have serious preexisting medical conditions. Have received treatment with a drug predominantly targeting Ang2 activity. Have symptomatic central nervous system (CNS) malignancy or metastasis. Have current hematologic malignancies. Have an active fungal, bacterial, and/or known viral infection. Have a corrected QT interval using Fridericia's correction (QTcF) of >470 msec on screening electrocardiogram (ECG) at several consecutive days of assessment. Have a known sensitivity to mAbs or other therapeutic proteins. Have a history of hypertensive crisis or hypertensive encephalopathy or current poorly controlled hypertension despite standard medical management. Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 3 months prior to receiving treatment. Receive anticoagulation therapy at therapeutic dose. Have experienced any arterial or venothrombotic or thromboembolic events within 6 months prior to study treatment. Have liver cirrhosis with a Child-Pugh class B or worse or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. The participant is pregnant prior to randomization or breastfeeding. The participant has sensory peripheral neuropathy ≥ Grade 2 (Part E only).

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A LY3127804<br>Dose escalation of LY3127804 given intravenously (IV) every 2 weeks (Q2W) for 28 day cycle. | Drug: LY3127804<br>* Administered IV<br>|
| Experimental: Part B LY3127804 + Ramucirumab Dose 1<br>Dose escalation of LY3127804 in combination with Ramucirumab given IV Q2W for 28 day cycle. | Drug: LY3127804<br>* Administered IV<br>Drug: Ramucirumab<br>* Administered IV<br>* Other names: 1121B;|
| Experimental: Part C LY3127804 + Ramucirumab Dose 2<br>LY3127804 in combination with Ramucirumab given IV Q2W for 28 day cycle. | Drug: LY3127804<br>* Administered IV<br>Drug: Ramucirumab<br>* Administered IV<br>* Other names: 1121B;|
| Experimental: Part D LY3127804 + Ramucirumab<br>LY3127804 and Ramucirumab given IV Q2W until participant qualifies for study discontinuation. | Drug: LY3127804<br>* Administered IV<br>Drug: Ramucirumab<br>* Administered IV<br>* Other names: 1121B;|
| Experimental: Part E LY3127804 + Ramucirumab + Paclitaxel<br>LY3127804 and Ramucirumab given IV Q2W and Paclitaxel given IV on day 1, 8, and 15 until participant qualifies for study discontinuation. | Drug: LY3127804<br>* Administered IV<br>Drug: Ramucirumab<br>* Administered IV<br>* Other names: 1121B;Drug: Paclitaxel<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) |  | Baseline through Cycle 1 (28 Day Cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Total Dose (MTD) of LY3127804 Monotherapy and in Combination with Ramuricumab +/- Paclitaxel |  | Baseline through Cycle 1 (28 Day Cycle) | 
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3127804 |  | Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 4 Months) | 
| Pharmacokinetics: AUC of Ramucirumab in Combination with LY3127804 +/- Paclitaxel |  | Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 4 Months) | 
| Number of Participants with Anti-LY3127804 Antibodies |  | Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 5 Months) | 
| Number of Participants with Anti-Ramucirumab Antibodies |  | Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 5 Months) | 
| Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] |  | Baseline through Measured Progressive Disease or Death (Estimated up to 4 Months) | 
| Progression Free Survival (PFS) |  | Baseline to Measured Progressive Disease or Death (Estimated up to 4 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced, Angiopoietin