A Study of LY3023414 and Necitumumab in Squamous Lung Cancer

Non-small Cell Lung Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02443337
• Other study ID #: 15799
• Secondary ID: I6A-MC-CBBE
• Status: Terminated
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: September 2017

Study information

• Verified date: January 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non-small Cell Lung Cancer Metastatic

Intervention

Drug:
• LY3023414
Administered orally
• Necitumumab
Administered IV

Locations

Country	Name	City	State
United States	Ironwood Cancer & Research Centers	Chandler	Arizona
United States	University of Virginia Health	Charlottesville	Virginia
United States	Chattanooga Oncology Hematology	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc.	Cincinnati	Ohio
United States	Comprehensive Cancer Care and Research Institute of Colorado	Englewood	Colorado
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Research Medical Center	Kansas City	Missouri
United States	Southern Cancer Center, P.C.	Mobile	Alabama
United States	SMO Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Tennessee Oncology	Nashville	Tennessee
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Palm Beach Cancer Institute	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	SCRI Development Innovations, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)