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

NCT ID: NCT02789345

Last Updated: 2024-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-24
• Study Completion Date: 2022-05-09

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Ramucirumab + Osimertinib

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.

Group Type: EXPERIMENTAL

Ramucirumab

Intervention Type: DRUG

Administered IV

Osimertinib

Intervention Type: DRUG

Administered orally

Arm B: Necitumumab + Osimertinib

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.

Group Type: EXPERIMENTAL

Necitumumab

Intervention Type: DRUG

Administered IV

Osimertinib

Intervention Type: DRUG

Administered orally

Cohort A: Ramucirumab + Osimertinib

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.

Group Type: EXPERIMENTAL

Ramucirumab

Intervention Type: DRUG

Administered IV

Osimertinib

Intervention Type: DRUG

Administered orally

Interventions

Ramucirumab

Administered IV

Intervention Type: DRUG

Necitumumab

Administered IV

Intervention Type: DRUG

Osimertinib

Administered orally

Intervention Type: DRUG

Other Intervention Names

LY3009806; LY3012211; AZD9291

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

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, , France

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, , South Korea

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, , South Korea

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, , South Korea

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, , South Korea

Hospital Universitario Ramon y Cajal

Madrid, , Spain

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, , Spain

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, , Spain

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 City, , Taiwan

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, , Taiwan

Countries

United States; France; South Korea; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 33046516 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/4jipcrdi0g6CmmMMe8mUyI

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

Other Identifiers

I4T-MC-JVDL

Identifier Type: OTHER

Identifier Source: secondary_id

2015-005296-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16357

Identifier Type: -

Identifier Source: org_study_id