A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer

ID: NCT02789345
Status: Recruiting
Phase: Phase 1
Start Date: October 24, 2016
First Submitted: May 31, 2016
Last Updated: February 23, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company, AstraZeneca
Location: France, Korea, Republic of, Spain, Taiwan, United States
Conditions: Non-small Cell Lung Cancer
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief Summary

The main purpose of this study is to evaluate the safety of ramucirumab or necitumumab in combination with osimertinib in participants with non-small cell lung cancer (NSCLC).

Detailed Description

Condition or disease Intervention/treatment Phase

Non-small Cell Lung Cancer

Drug: Ramucirumab
Other Names
LY3009806
Drug: Necitumumab
Other Names
LY3012211
Drug: Osimertinib
Other Names
AZD9291
Phase 1

Tracking Information

First Submitted DateMay 31, 2016
Last Update Posted DateFebruary 23, 2018
Actual Start DateOctober 24, 2016
Anticipated Completion DateMay 01, 2019
Actual Primary Completion DateOctober 19, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of Participants with Dose Limiting Toxicities (DLTs) [Time Frame: Up to Two Cycles (Up to 21 Day Cycles)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [Time Frame: Day 1 Cycle 2 to Day 1 Cycle 13 (14 Day Cycles)]

  • PK: Cmin of Necitumumab [Time Frame: Day 1 Cycle 3 to Day 1 Cycle 9 (21 Day Cycles)]

  • Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) [Time Frame: Baseline to Objective Disease Progression (Approximately 30 Months)]

  • Disease Control Rate (DCR): Percentage of Participants with CR, PR or Stable Disease (SD) [Time Frame: Baseline to Objective Disease Progression (Approximately 30 Months)]

  • Duration of Response (DoR) [Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Approximately 30 Months)]

  • Progression Free Survival (PFS) [Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Approximately 30 Months)]

  • Overall Survival (OS) [Time Frame: Baseline to Death from Any Cause (Approximately 30 Months)]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer
Official TitleAn Open-Label, Multicenter, Phase 1 Study With Expansion Cohorts of Ramucirumab or Necitumumab in Combination With Osimertinib in Patients With Advanced T790M-Positive EGFR-Mutant Non-Small Cell Lung Cancer After Progression on First-Line EGFR TKI Therapy
Brief Summary

The main purpose of this study is to evaluate the safety of ramucirumab or necitumumab in combination with osimertinib in participants with non-small cell lung cancer (NSCLC).

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
74
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Non-small Cell Lung Cancer
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Ramucirumab

Administered IV

Other Names
LY3009806
Drug: Necitumumab

Administered IV

Other Names
LY3012211
Drug: Osimertinib

Administered orally

Other Names
AZD9291
Study Groups/Cohorts
Ramucirumab + Osimertinib
Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.

Necitumumab + Osimertinib
Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.

Study Arms
Experimental Necitumumab + Osimertinib
Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.
Drug : Necitumumab
Administered IV

Experimental Necitumumab + Osimertinib
Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.
Drug : Osimertinib
Administered orally

Experimental Ramucirumab + Osimertinib
Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.
Drug : Ramucirumab
Administered IV

Experimental Ramucirumab + Osimertinib
Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.
Drug : Osimertinib
Administered orally

Arm Intervention/Treatment
Experimental Necitumumab + Osimertinib
Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.
Drug : Necitumumab
Experimental Necitumumab + Osimertinib
Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.
Drug : Osimertinib
Experimental Ramucirumab + Osimertinib
Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.
Drug : Ramucirumab
Experimental Ramucirumab + Osimertinib
Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.
Drug : Osimertinib

Recruitment Information

Recruitment Status:Recruiting
Enrollment74
Completion DateMay 01, 2019
Eligibility Criteria: Inclusion Criteria:
- Have a diagnosis of NSCLC with at least 1 measurable lesion assessable using standard techniques by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
- Have T790M-positive status using a test validated and performed locally after disease progression on EGFR tyrosine kinase inhibitor (TKI) treatment.
- Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the time of enrollment.
- Have serum albumin that is ≥25 grams per liter at the time of enrollment.
- Have adequate organ function, with all screening labs performed within 7 days of treatment initiation.
- Have a life expectancy of ≥3 months.
- Have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Exclusion Criteria:
- Previous treatment with an EGFR monoclonal antibody (except for past treatment for squamous cell carcinoma of head and neck or metastatic colorectal cancer).
- Previous treatment with osimertinib or third generation EGFR TKIs.
- Participants with symptomatic or growing brain metastases less than 4 weeks prior to enrollment.
- History of drug-induced interstitial lung disease (ILD), ILD, or radiation pneumonitis requiring treatment with steroid prior to study enrollment, or any evidence of clinically active ILD.
- Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment. Participants with a history of gross hemoptysis (defined as bright red blood of ≥1/2 teaspoon) within 2 months prior to enrollment are excluded.
- Have experienced any arterial thrombotic event or arterial thromboembolic event, including myocardial infarction, unstable angina (history or evidence of current clinically relevant coronary artery disease of current ≥Class III as defined by Canadian Cardiovascular Society Angina Grading Scale or congestive heart failure of current ≥Class III as defined by the New York Heart Association), cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
- Have a history of deep vein thrombosis, pulmonary embolism, or any other significant venous thromboembolism (venous catheter thrombosis or superficial venous thrombosis not considered "significant") during the 3 months prior to study enrollment. Participants with venous thromboembolism occurring 3 to 6 months prior to study enrollment are allowed, if being treated with low molecular weight heparin.
- Have a history of gastrointestinal perforation and/or fistula within 6 months prior to enrollment.
- Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
- Have uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating study treatment, despite antihypertensive intervention. CTCAE Version 4.0 defines uncontrolled hypertension as Grade >2 hypertension; clinically, the participant continues to experience elevated blood pressure (systolic >160 millimeters of mercury [mmHg] and/or diastolic >100 mmHg) despite medications.
- Are receiving chronic therapy with any of the following medications within 7 days prior to enrollment:
- nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents).
- other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide).
- Have radiologically documented evidence of major blood vessel invasion or encasement by cancer.
- Have radiographic evidence of pulmonary intratumor cavitation, regardless of tumor histology.
- Are receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks prior to enrollment.
- Have abnormal cardiac findings.
- Have undergone chest irradiation within 2 weeks prior to study drug administration, have not recovered from all radiation-related toxicities, or requires corticosteroids. A 2-week washout is permitted for focal palliative radiation to non-central nervous system disease.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
France
Korea, Republic of
Spain
Taiwan
United States
Hong Kong
Italy

Administrative Information

NCT Number:NCT02789345
Other Study ID Numbers
16357
I4T-MC-JVDL
2015-005296-25
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
AstraZeneca
Investigators
Study Director
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