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
Overview
- Phase
- Phase 2
- Intervention
- LY3023414
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Sponsor
- Eli Lilly and Company
- Enrollment
- 31
- Locations
- 13
- Primary Endpoint
- Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief 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).
Investigators
Eligibility Criteria
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.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •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
- •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
- •Concurrent serious infection requiring parenteral antibiotic therapy.
Arms & Interventions
LY3023414 + Necitumumab
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.
Intervention: LY3023414
LY3023414 + Necitumumab
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.
Intervention: Necitumumab
Outcomes
Primary Outcomes
Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR)
Time Frame: 6 Months
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.
Secondary Outcomes
- Pharmacokinetics (PK): 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)
- Overall Survival (OS)(Enrollment to Death from Any Cause (Up To 16 Months))
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)(Baseline to Objective Disease Progression or Initiation of Subsequent Anticancer Therapy (Up To 3 Months))
- Progression Free Survival (PFS)(Enrollment to Measured Progressive Disease or Death from Any Cause (Up To 12 Months))
- Pharmacokinetics: 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))