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Non-small Cell Lung CancerPhase 1NCT02789345

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

A Phase 1 study testing Ramucirumab, Necitumumab and Osimertinib in people with Non-small Cell Lung Cancer, run by Eli Lilly and Company at 11 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Ramucirumab, Necitumumab and Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
11 sitesin 5 countries
Study dates
24 Oct 2016to 9 May 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

11 sites in 5 countries.

11 sites in 5 countries

South Korea4 sites

  • 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

  • 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

  • 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

  • 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

Other trials in South Korea

Spain3 sites

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • 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

  • 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

Other trials in Spain

Taiwan2 sites

  • 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

  • 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

Other trials in Taiwan

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

France1 site

  • 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

Other trials in France

About this study

Official title: An 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

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).

Being tested
Ramucirumab, Necitumumab, Osimertinib
Keywords
T790M, epidermal growth factor receptor (EGFR)
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RamucirumabDrug

    Also called LY3009806

    Administered IV

  • NecitumumabDrug

    Also called LY3012211

    Administered IV

  • OsimertinibDrug

    Also called AZD9291

    Administered orally

Study groups in NCT02789345
Study groupRoleWhat they receive
Arm A: Ramucirumab + OsimertinibExperimentalDose 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.
Receives: Drug: Ramucirumab; Drug: Osimertinib
Arm B: Necitumumab + OsimertinibExperimentalDose 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.
Receives: Drug: Necitumumab; Drug: Osimertinib
Cohort A: Ramucirumab + OsimertinibExperimentalDose 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.
Receives: Drug: Ramucirumab; Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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:
    3. Grade 4 toxicity lasting ≥7 days, or
    4. Grade 3 or 4 thrombocytopenia if associated with bleeding or requires platelet transfusion, or
    5. Febrile neutropenia
    6. Death if considered related to study treatment
    7. Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting

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

Secondary outcomes (7)

  1. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

    Cmin was the concentration of study drug in the blood immediately before the next dose was administered.

    Measured: 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

  2. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab

    Cmin was the concentration of study drug in the blood immediately before the next dose was administered.

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

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

    ORR was the best overall response of complete response (CR) or partial response (PR) as classified by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR was a disappearance of all target and non-target lesions and normalization of tumor marker level. PR was an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

    Measured: Baseline to Objective Disease Progression (up to 25 months)

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

    DCR was the best overall response of CR, PR, or SD as defined by RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or one or more new lesions.

    Measured: Baseline to Objective Disease Progression (up to 25 months)

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

    Duration of Response (DoR) was defined only for participants with a confirmed CR or PR. It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date, DOR was censored at the date of the last complete objective progression-free disease assessment.

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

  6. Progression Free Survival (PFS) for Ramucirumab in Combination With Osimertinib

    Progression-free survival (PFS) was the time from the date of first study treatment until the date of radiographic documentation of progression (as defined by RECIST v. 1.1) based on investigator assessment or the date of death due to any cause, whichever was earlier. If a participant did not have a complete baseline disease assessment, then the PFS time was censored at the enrollment date, regardless of whether or not objectively determined disease progression or death was observed for the participant; otherwise, if a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last complete objective progression-free disease assessment date.

    Measured: Baseline to Measured Progressive Disease or Death from Any Cause (up to 26 months)

  7. Overall Survival (OS) for Ramucirumab in Combination With Osimertinib

    OS was date of first study treatment until death due to any cause. If the participant was alive at the data inclusion cutoff date for the analysis (or was lost to follow-up), OS was censored on the last date the participant was known to be alive.

    Measured: Baseline to Death from Any Cause (up to 29 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2016 (estimated)
  2. Study start24 Oct 2016
  3. Primary completion19 Oct 2017
  4. Study completion9 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02789345
Sponsor's protocol ID
16357
Other IDs
I4T-MC-JVDL, 2015-005296-25, 2015
Status last verified
May 2023
First submitted
31 May 2016
Last updated
5 Feb 2024
Data monitoring committee
No

Publications

  • 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.

    PubMed 33046516

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ramucirumab, Necitumumab and Osimertinib in people with Non-small Cell Lung Cancer, run by Eli Lilly and Company at 11 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in South Korea, Spain, Taiwan, United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Arm A: Cycle 1 through Cycle 2 (14-day cycle); Arm B: Cycle 1 (21-day cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02789345, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2024.

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