Clinical trial NCT02789345: A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: T790M
epidermal growth factor receptor (EGFR)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2016-06-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Arm A: Cycle 1 through Cycle 2 (14-day cycle); Arm B: Cycle 1 (21-day cycle)
Secondary outcomes:
measure: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
timeFrame: 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
measure: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
timeFrame: Predose on Day 1 of Cycle 3, Predose on Day 1 of Cycle 5
measure: Objective Response Rate (ORR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline to Objective Disease Progression (up to 25 months)
measure: Disease Control Rate (DCR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With CR, PR or Stable Disease (SD)
timeFrame: Baseline to Objective Disease Progression (up to 25 months)
measure: Duration of Response (DoR) for Ramucirumab in Combination With Osimertinib
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (up to 25 months)
measure: Progression Free Survival (PFS) for Ramucirumab in Combination With Osimertinib
timeFrame: Baseline to Measured Progressive Disease or Death from Any Cause (up to 26 months)
measure: Overall Survival (OS) for Ramucirumab in Combination With Osimertinib
timeFrame: Baseline to Death from Any Cause (up to 29 months)
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Villejuif
country: France
facility: 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.
city: Cheong Ju-City
country: Korea, Republic of
facility: 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.
city: Seongnam
country: Korea, Republic of
facility: 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.
city: Seoul
country: Korea, Republic of
facility: 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.
city: Seoul
country: Korea, Republic of
facility: 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.
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: 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.
city: Sevilla
country: Spain
facility: 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.
city: Tainan
country: Taiwan
facility: 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.
city: Taipei city
country: Taiwan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
citation: 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.