A Randomized, Multicenter, Open-Label Phase 3 Study of Pemetrexed-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Pemetrexed-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 633
- Locations
- 2
- Primary Endpoint
- Overall Survival Time (OS)
Study Overview
Brief Summary
The research study is testing the investigational drug necitumumab in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and pemetrexed will be more effective in improving participant disease than the standard chemotherapy combination alone.
Detailed Description
Multinational, randomized, multicenter, open-label Phase 3 study of 633 participants with advanced, nonsquamous (Stage IV) NSCLC. Participants will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of pemetrexed and cisplatin in study Arm A, or first-line pemetrexed-cisplatin chemotherapy alone in Arm B.
Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization).
Participants will undergo radiographic assessment (computed tomography or magnetic resonance imaging) of disease status every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (Or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); participants in Arm A only will continue to receive necitumumab until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For participants who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the participant is alive, or until the end of the trial.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Has histologically or cytologically confirmed nonsquamous (adenocarcinoma/large cell or other) non small cell lung cancer
- •Has Stage IV disease at the time of study entry
- •Measurable or nonmeasurable disease (as defined by the Response Evaluation Criteria in Solid Tumors RECIST 1.0) at the time of study entry (participants with only truly nonmeasurable disease are not eligible)
- •Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
- •Has an Eastern Cooperative Oncology Group performance status score of 0-2
- •Has adequate hepatic function
- •Has adequate renal function
- •Has adequate hematologic function
- •If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method). If male, the participants surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
- •Female participants of childbearing potential must have a negative serum
Exclusion Criteria
- •Has squamous non small cell lung cancer
- •Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the Epidermal Growth Factor Hormone (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor
- •Received previous chemotherapy for advanced NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
- •Undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
- •Undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
- •Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
- •Has superior vena cava syndrome contraindicating hydration
- •Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
- •Has experienced myocardial infarction within 6 months prior to randomization
- •Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
- •Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder, potentially precluding protocol compliance
- •Has Grade ≥ 2 peripheral neuropathy
- •Has significant third space fluid retention, requiring repeated drainage
- •Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the participant's ability to complete the study or sign an informed consent document The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of IMC-11F8, or any other contraindication to one of the administered treatments
- •Is pregnant or breastfeeding
- •Has a known history of drug abuse
- •Has a concurrent active malignancy other than adequately-treated basal cell carcinoma of the skin or preinvasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
Arms & Interventions
Necitumumab + Pemetrexed + Cisplatin
Necitumumab + Pemetrexed + Cisplatin
Intervention: Pemetrexed (Drug)
Necitumumab + Pemetrexed + Cisplatin
Necitumumab + Pemetrexed + Cisplatin
Intervention: Cisplatin (Drug)
Necitumumab + Pemetrexed + Cisplatin
Necitumumab + Pemetrexed + Cisplatin
Intervention: Necitumumab (Biological)
Pemetrexed + Cisplatin
Pemetrexed + Cisplatin
Intervention: Pemetrexed (Drug)
Pemetrexed + Cisplatin
Pemetrexed + Cisplatin
Intervention: Cisplatin (Drug)
Outcomes
Primary Outcomes
Overall Survival Time (OS)
Time Frame: Randomization to Death from Any Cause (Up to 31.6 Months)
OS is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.
Secondary Outcomes
- Progression-Free Survival (PFS)(Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months))
- Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate [ORR])(Baseline to Measured Progressive Disease (Up to 30.4 Months))
- Time to Treatment Failure (TTF)(Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months))
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab(Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks)
- Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)(Baseline to Study Completion (Up to 31.6 Months))
- Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (EQ-5D)(Baseline, Cycle 6 (Cycle = 3 weeks))
- Mean Change From Baseline in PRO as Measured Using the Lung Cancer Symptom Scale (LCSS)(Baseline, Cycle 6 (Cycle =3 Weeks))
- Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)(Baseline)
- Percentage of Participants With EGFR Measured by IHC(Baseline)