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

NCT02789345 | Completed Phase 1 Results

• 3 other identifiers: 16357I4T-MC-JVDL2015-005296-25
• Study Type: interventional
• Target: 29
• Locations: 5 countries
• Sites: 11

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).

Conditions

Non-small Cell Lung Cancer

Keywords

T790M; epidermal growth factor receptor (EGFR)

Outcome Measures

Primary Outcomes (1)

• Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)

  A Dose Limiting Toxicity (DLT) was defined as one of the following Adverse Events (AE) that is likely related to the study drug or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: 1. Any nonhematologic Grade ≥3 toxicity, except for toxicities such as liver or renal function abnormality, skin rash that resolves with appropriate therapy, transient hypersensitivity and injection site reactions, myalgia, fatigue, constipation, electrolyte imbalance, nausea, vomiting, diarrhea 2. Hematologic toxicity was considered a DLT as the following: 1. Grade 4 toxicity lasting ≥7 days, or 2. Grade 3 or 4 thrombocytopenia if associated with bleeding or requires platelet transfusion, or 3. Febrile neutropenia 3. Death if considered related to study treatment 4. Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting

  Arm A: Cycle 1 through Cycle 2 (14-day cycle); Arm B: Cycle 1 (21-day cycle)

Secondary Outcomes (7)

• Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

  Predose on Day (D) 1 of Cycle (C) 2, Predose on Day 1 of Cycle 4, Predose on Day 1 of Cycle 5, Predose on Day 1 of Cycle 7, Predose on Day 1 of Cycle 13

• Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab

  Predose on Day 1 of Cycle 3, Predose on Day 1 of Cycle 5

• Objective Response Rate (ORR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With a Complete Response (CR) or Partial Response (PR)

  Baseline to Objective Disease Progression (up to 25 months)

• Disease Control Rate (DCR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With CR, PR or Stable Disease (SD)

  Baseline to Objective Disease Progression (up to 25 months)

• Duration of Response (DoR) for Ramucirumab in Combination With Osimertinib

  Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (up to 25 months)

Study Arms (3)

Arm A: Ramucirumab + Osimertinib

EXPERIMENTAL

Dose Finding: Participants received Ramucirumab 10 milligrams/kilogram (mg/kg) given intravenously (IV) on day 1 every 2 weeks and osimertinib 80 milligrams (mg) given orally daily during each 14-day cycle.

Drug: Ramucirumab; Drug: Osimertinib

Arm B: Necitumumab + Osimertinib

EXPERIMENTAL

Dose Finding: Participants received Necitumumab 800 mg given IV on days 1 and 8 every 3 weeks and osimertinib 80 mg given orally daily during each 21 day cycle.

Drug: Necitumumab; Drug: Osimertinib

Cohort A: Ramucirumab + Osimertinib

EXPERIMENTAL

Dose Expansion: Participants received Ramucirumab 10 mg/kg given IV on day 1 every 2 weeks and osimertinib 80 mg given orally daily during each 14-day cycle.

Drug: Ramucirumab; Drug: Osimertinib

Interventions

Ramucirumab DRUG

Administered IV

Also known as: LY3009806

Arm A: Ramucirumab + Osimertinib; Cohort A: Ramucirumab + Osimertinib

Necitumumab DRUG

Administered IV

Also known as: LY3012211

Arm B: Necitumumab + Osimertinib

Osimertinib DRUG

Administered orally

Also known as: AZD9291

Arm A: Ramucirumab + Osimertinib; Arm B: Necitumumab + Osimertinib; Cohort A: Ramucirumab + Osimertinib

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• AstraZeneca: collaborator

Study Sites (11)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, 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.

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.

Cheong Ju-City, 28644, South Korea

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.

Seongnam, 13496, South Korea

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.

Seoul, 05505, South Korea

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.

Seoul, 06351, South Korea

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

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.

Madrid, 28041, Spain

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.

Seville, 41013, Spain

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.

Tainan, 70403, Taiwan

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.

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Yu HA, Paz-Ares LG, Yang JC, Lee KH, Garrido P, Park K, Kim JH, Lee DH, Mao H, Wijayawardana SR, Gao L, Hozak RR, Chao BH, Planchard D. Phase I Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-positive EGFR-mutant Non-small Cell Lung Cancer. Clin Cancer Res. 2021 Feb 15;27(4):992-1002. doi: 10.1158/1078-0432.CCR-20-1690. Epub 2020 Oct 12.

  PMID: 33046516 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ramucirumab; necitumumab; osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: May 31, 2016
• First Posted: June 3, 2016
• Study Start: October 24, 2016
• Primary Completion: October 19, 2017
• Study Completion: May 9, 2022
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2023-05

Locations

ES (3); KR (4); TW (2); US (1); FR (1)