Phase 1
Completed N=29
A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer
Source: ClinicalTrials.gov NCT02789345 ↗Enrolled (actual)
29
Serious AEs
34.5%
Results posted
Feb 2024
Primary outcomePrimary: Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0 | — |
| SECONDARY Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab |
41.3; 66.7; 76.7; 90.7; 103 | — |
| SECONDARY Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab |
NA; NA | — |
| SECONDARY Objective Response Rate (ORR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With a Complete Response (CR) or Partial Response (PR) |
76 | — |
| SECONDARY Disease Control Rate (DCR) for Ramucirumab in Combination With Osimertinib: Percentage of Participants With CR, PR or Stable Disease (SD) |
92 | — |
| SECONDARY Duration of Response (DoR) for Ramucirumab in Combination With Osimertinib |
13.37 | — |
| SECONDARY Progression Free Survival (PFS) for Ramucirumab in Combination With Osimertinib |
11.04 | — |
| SECONDARY Overall Survival (OS) for Ramucirumab in Combination With Osimertinib |
NA | — |
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 chemo
Data sourced from ClinicalTrials.gov (NCT02789345). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.