A Study of LY3023414 and Necitumumab in Squamous Lung Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and activity of the study drug known as LY3023414 in combination with necitumumab in participants with metastatic squamous non-small cell lung cancer (NSCLC).

Official Title
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A Phase II Study of the Combination of LY3023414 and Necitumumab After First-Line Chemotherapy for Metastatic Squamous Non-small Cell Carcinoma of the Lung

Conditions
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Non-small Cell Lung Cancer Metastatic

Intervention / Treatment
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* Drug: LY3023414
* Drug: Necitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous advanced NSCLC (Stage IV). Participants must have progressed on one prior line of platinum-based chemotherapy in the advanced or metastatic setting. Measurable disease as measured by response evaluation criteria in solid tumors (RECIST) criteria v 1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Able to swallow the study drugs whole. Adequate organ function. Women of childbearing potential must have a negative serum or urine pregnancy test performed ≤ 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment and during the 3 months following completion of study treatment. Exclusion Criteria: Participants who have received > 1 prior line of chemotherapy in the advanced or metastatic setting. (Immunotherapy will not be considered a line of chemotherapy.) Prior treatment with a PI3K/mTOR inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and/or necitumumab. History of brain metastases unless irradiated ≥ 2 weeks prior to first study treatment and stable without requirement of corticosteroids. Have serious pre-existing medical conditions. Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics. Women who are pregnant or breast-feeding. Clinically significant electrolyte imbalance ≥ Grade 2. Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin and oral Xa inhibitors are allowed. Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) ≤ 28 days prior to Day 1 of Cycle 1. Concurrent serious infection requiring parenteral antibiotic therapy. Have a second primary malignancy that in the judgment of the investigator and Medical Monitor may affect the interpretation of results. Have an active, known fungal, bacterial, and/or known viral infection. History of arterial or venous embolism within 3 months prior to study enrollment. If the embolism occurred >3 and <6 months, the participant is eligible provided appropriate treatment according to institutional standard of care is ensured.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3023414 + Necitumumab<br>200 milligrams (mg) LY3023414 administered orally twice daily and 800 mg necitumumab administered intravenously (IV) on day 1 and day 8 of each cycle (21 day cycles). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: LY3023414<br>* Administered orally<br>Drug: Necitumumab<br>* Administered IV<br>* Other names: IMC-11F8;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR) | RECIST v 1.1 was used to assess tumor response.The 6-month DCR was defined as the number of participants with PFS > 6 months (or 26 weeks, to accommodate the scheduled tumor assessment at week 24 be delayed by up to 2 weeks) divided by number of participants with baseline tumor assessment. Target Lesions:CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest (nadir) sum of diameters since the treatment started. Non-Target Lesions:CR was defined as disappearance of all non-target lesions and normalization of tumor markers.All lymph nodes must be non-pathological in size (<10 millimeters(mm) short axis).SD was defined as the persistence of one or more non-target lesions and/or persistence of tumor marker level above the normal limits. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) | RECIST v 1.1 was used to assess tumor response. ORR for a given participant was based on objective responses determined from data obtained up to: progression, the last evaluable assessment in the absence of progression, or initiation of subsequent anticancer therapy. Participants for whom an objective response cannot be determined or for who the best objective response is not evaluable (NE) were considered non-responders. Target Lesions: CR was defined as the disappearance of all target lesions. PR was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesions: CR was defined as disappearance of all non-target lesions and normalization of tumor markers. All lymph nodes must be non-pathological in size (<10 mm short axis). The ORR percentage was calculated as the number of participants with best objective response of CR or PR divided by the number of participants with measurable disease at baseline. | Baseline to Objective Disease Progression or Initiation of Subsequent Anticancer Therapy (Up To 3 Months) | 
| Progression Free Survival (PFS) | PFS was defined as the time from enrollment until the date of disease progression per RECIST v 1.1 or death by any cause.Participants who had not progressed or died at the time of assessment were censored at the time of the last date of tumor assessment.Participants who are enrolled but do not receive treatment and participants who have no evaluable visits will be censored on day 1.Participants who received new anti-cancer therapy before disease progression or death will be censored to the last tumor assessment date prior to the new anti-cancer therapy. Target Lesions:PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest(nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. Non-Target Lesions(NTL):PD is defined as appearance of one or more new lesions and/or unequivocal progression of existing NTL. | Enrollment to Measured Progressive Disease or Death from Any Cause (Up To 12 Months) | 
| Overall Survival (OS) | OS was defined as the time from enrollment until the date of death by any cause. Participants lost follow up or did not die at the time of assessment were censored at the time of the last known alive date. | Enrollment to Death from Any Cause (Up To 16 Months) | 
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab | Minimum Concentration (Cmin) of LY3023414 and Necitumumab | Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion), Cycle 2 Day 1, Cycle 4 Day 1 | 
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3023414 and Necitumumab | Maximum Concentration (Cmax) of LY3023414 and Necitumumab | Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion) |