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

Lilly

Status and phase: Terminated; Phase 1

Conditions: Solid Tumors

Treatments: Drug: LY3127804; Drug: Ramucirumab; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT02597036

2015-001204-64 (EudraCT Number)

I7W-MC-JQBA (Other Identifier)

15580

Details and patient eligibility

About

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

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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62 participants in 5 patient groups

Part A LY3127804

Experimental group

Description:

Participants received escalating doses of 4 milligram per kilogram (mg/kg), 8 mg/kg, 12 mg/kg, 16 mg/kg, 20 mg/kg and 27 mg/kg LY3127804 administered as intravenous (IV) infusion on days 1 and 15 of a 28-day cycle.

Treatment:

Drug: LY3127804

Part B LY3127804 + 8 mg/kg Ramucirumab

Experimental group

Description:

Participants received escalating doses of 8 mg/kg / 12 mg/kg / 16 mg/kg / 20 mg/kg / 27 mg/kg LY3127804 plus 8 mg/kg ramucirumab administered as IV infusion on days 1 and 15 of a 28-day cycle.

Treatment:

Drug: Ramucirumab

Drug: LY3127804

Part C LY3127804 + 12 mg/kg Ramucirumab

Experimental group

Description:

Participants received 20 mg/kg LY3127804 plus 12 mg/kg ramucirumab administered as IV infusion on days 1 and 15 of a 28-day cycle.

Treatment:

Drug: Ramucirumab

Drug: LY3127804

Part D LY3127804 + Ramucirumab - Not Enrolled

Experimental group

Description:

Participants were to receive LY3127804 and Ramucirumab IV Q2W until participant qualifies for study discontinuation. Part D and E were not enrolled based on the primary and secondary outcomes/ results of Part A-C.

Treatment:

Drug: Ramucirumab

Drug: LY3127804

Part E LY3127804 + Ramucirumab + Paclitaxel - Not Enrolled

Experimental group

Description:

Participants were to receive LY3127804 and Ramucirumab IV Q2W and Paclitaxel IV on day 1, 8, and 15 until participant qualifies for study discontinuation. Part D and E were not enrolled based on the primary and secondary outcomes/ results of Part A-C.

Treatment:

Drug: Paclitaxel

Drug: Ramucirumab

Drug: LY3127804