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

NCT02597036 | Terminated Phase 1 Results

• 3 other identifiers: 15580I7W-MC-JQBA2015-001204-64
• Study Type: interventional
• Target: 62
• Locations: 4 countries
• Sites: 5

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

Conditions

Solid Tumors

Keywords

Advanced, Angiopoietin

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 Dose of LY3127804 Monotherapy and in Combination With Ramucirumab

  Recommended Phase 2 dose was determined based on observed safety, pharmacokinetics (PK) and efficacy. However maximum tolerated dose (MTD) was not determined. For the purpose of this study, the MTD is defined as the highest tested dose in a single-agent setting that has less than (\<) 33% probability of causing a DLT. MTD in the combination setting was determined based on the nature and timing of the DLTs in the combination setting. Dose-limiting toxicities were not reported in any treatment cohort. Therefore, the maximum tolerated LY3127804 dose could not be determined.

  Baseline through Cycle 1 (28 Day Cycle)

Secondary Outcomes (7)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  Baseline through Cycle 1 (28 Day Cycle)

• Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3127804

  predose, end of infusion (1h), 2h, 24h, 96h, 168h, 336 h following dose on day 1 and at predose, end of infusion (1h), 24h, 168h and 336 h following dose on day 15 and at predose, end of infusion (1h), 2h, 168h, 336h following dose on day 29

• Pharmacokinetics: AUC of Ramucirumab in Combination With LY3127804

  predose, end of infusion (1h), 24h, 96h, 168h, 336 h following Ramucirumab dose on day 1

• Number of Participants With Anti-LY3127804 Antibodies

  Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Up To 5 Months)

• Number of Participants With Anti-Ramucirumab Antibodies

  Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Up to 5 Months)

Study Arms (5)

Part A LY3127804

EXPERIMENTAL

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.

Drug: LY3127804

Part B LY3127804 + 8 mg/kg Ramucirumab

EXPERIMENTAL

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.

Drug: LY3127804; Drug: Ramucirumab

Part C LY3127804 + 12 mg/kg Ramucirumab

EXPERIMENTAL

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.

Drug: LY3127804; Drug: Ramucirumab

Part D LY3127804 + Ramucirumab - Not Enrolled

EXPERIMENTAL

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.

Drug: LY3127804; Drug: Ramucirumab

Part E LY3127804 + Ramucirumab + Paclitaxel - Not Enrolled

EXPERIMENTAL

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.

Drug: LY3127804; Drug: Ramucirumab; Drug: Paclitaxel

Interventions

LY3127804 DRUG

Administered IV

Part A LY3127804; Part B LY3127804 + 8 mg/kg Ramucirumab; Part C LY3127804 + 12 mg/kg Ramucirumab; Part D LY3127804 + Ramucirumab - Not Enrolled; Part E LY3127804 + Ramucirumab + Paclitaxel - Not Enrolled

Ramucirumab DRUG

Administered IV

Also known as: LY3009806, Cyramza, 1121B

Part B LY3127804 + 8 mg/kg Ramucirumab; Part C LY3127804 + 12 mg/kg Ramucirumab; Part D LY3127804 + Ramucirumab - Not Enrolled; Part E LY3127804 + Ramucirumab + Paclitaxel - Not Enrolled

Paclitaxel DRUG

Administered IV

Part E LY3127804 + Ramucirumab + Paclitaxel - Not Enrolled

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

SMO Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

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.

Brussels, 1000, Belgium

Location

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.

Villejuif, 94805, France

Location

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.

Barcelona, 08035, Spain

Location

Related Publications (1)

• 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.

  PMID: 32741971 DERIVED

Related Links

• A Study of LY3127804 with Ramucirumab in Participants with Advanced Solid Tumors

MeSH Terms

Interventions

zansecimab; Ramucirumab; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

No participants were enrolled in Part D and Part E reporting arms as these were deleted from protocol last amendment (based on the primary and secondary outcomes/ results of Part A-C).

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: November 6, 2015
• Primary Completion: November 23, 2017
• Study Completion: May 24, 2020
• Last Updated: October 23, 2025
• Results First Posted: October 23, 2025

Record last verified: 2025-10

Locations

BE (1); FR (1); US (2); ES (1)