Clinical trial NCT02597036: A Study of LY3127804 With Ramucirumab in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study of LY3127804 as Monotherapy and in Combination With Ramucirumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Advanced, Angiopoietin
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-11-04
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (28 Day Cycle)
Secondary outcomes:
measure: Maximum Total Dose (MTD) of LY3127804 Monotherapy and in Combination with Ramuricumab +/- Paclitaxel
timeFrame: Baseline through Cycle 1 (28 Day Cycle)
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3127804
timeFrame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 4 Months)
measure: Pharmacokinetics: AUC of Ramucirumab in Combination with LY3127804 +/- Paclitaxel
timeFrame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 4 Months)
measure: Number of Participants with Anti-LY3127804 Antibodies
timeFrame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 5 Months)
measure: Number of Participants with Anti-Ramucirumab Antibodies
timeFrame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Estimated up to 5 Months)
measure: Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
timeFrame: Baseline through Measured Progressive Disease or Death (Estimated up to 4 Months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Measured Progressive Disease or Death (Estimated up to 4 Months)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SMO Sarah Cannon Research Inst.
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Brussel
country: Belgium
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Villejuif
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Barcelona
country: Spain
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Martin-Liberal J, Hollebecque A, Aftimos P, Jungels C, Martin-Romano P, Rodon J, Kremer JD, Zhang W, Bendell J. First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours. Br J Cancer. 2020 Oct;123(8):1235-1243. doi: 10.1038/s41416-020-1011-7. Epub 2020 Aug 3.