Trial Outcomes & Findings for A Study of LY3023414 and Necitumumab in Squamous Lung Cancer (NCT NCT02443337)

Last Updated: 2020-12-09

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

6 Months

Results posted on

2020-12-09

Participant Flow

Participants completed the study if they had objective progressive disease (PD), stable disease (SD), complete response (CR) or partial response (PR).

Participant milestones

Participant milestones
Measure	Lead in Cohort 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.	Post Lead in Cohort 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.
Overall Study STARTED	15	16
Overall Study Received at Least One Dose of Study Drug	15	16
Overall Study COMPLETED	10	14
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Lead in Cohort 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.	Post Lead in Cohort 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.
Overall Study Adverse Event	0	1
Overall Study Clinical Progressive Disease	3	0
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

A Study of LY3023414 and Necitumumab in Squamous Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 Participants 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.	Total n=31 Participants Total of all reporting groups
Age, Continuous	66.0 years STANDARD_DEVIATION 10.18 • n=5 Participants	68.1 years STANDARD_DEVIATION 5.77 • n=7 Participants	67.1 years STANDARD_DEVIATION 8.13 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Months

Population: All participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 Participants 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.
Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at 6 Months: Disease Control Rate (DCR)	6.6 percentage of participants Interval 0.2 to 31.9	25.0 percentage of participants Interval 7.3 to 52.4

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Initiation of Subsequent Anticancer Therapy (Up To 3 Months)

Population: All participants who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 Participants 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.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)	0.00 percentage of participants Interval 0.0 to 21.8	0.00 percentage of participants Interval 0.0 to 20.6

SECONDARY outcome

Timeframe: Enrollment to Measured Progressive Disease or Death from Any Cause (Up To 12 Months)

Population: All participants who received at least one dose of study drug. Participants censored: Lead in Cohort 1 LY3023414 + Necitumumab= 4 and Post Lead in Cohort LY3023414 + Necitumumab=3

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.

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 Participants 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.
Progression Free Survival (PFS)	81 Days Interval 35.0 to 168.0	81 Days Interval 36.0 to 206.0

SECONDARY outcome

Timeframe: Enrollment to Death from Any Cause (Up To 16 Months)

Population: All participants who received at least one dose of study drug. Participants censored: Lead in Cohort 1 LY3023414 + Necitumumab=4 and Post Lead in Cohort LY3023414 + Necitumumab=9

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.

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 Participants 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.
Overall Survival (OS)	102 Days Interval 57.0 to 285.0	279 Days Interval 85.0 to The study was terminated early and therefore participants were not followed long enough to determine the upper level of the confidence Interval.

SECONDARY outcome

Timeframe: 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

Population: All participants who received at least one dose of study drug and had evaluable PK data.

Minimum Concentration (Cmin) of LY3023414 and Necitumumab

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=17 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=26 Participants 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.
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab Cycle 1 Day 8	14 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 172	69500 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 28
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab Cycle 2 day 1	NA Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA LY3023414 samples were below limit of quantification because only predose samples were collected.	54000 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 60
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab Cycle 3 Day8	9.73 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 221	121000 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 36
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3023414 and Necitumumab Cycle 4 Day 1	NA Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA LY3023414 samples were below limit of quantification because only predose samples were collected.	104000 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 56

SECONDARY outcome

Timeframe: Cycle 1 Day 8, and Cycle 3 Day 8 (pre-dose, end of necitumumab infusion and 1 hour post-necitumumab infusion)

Population: All participants who received at least one dose of study drug and had evaluable PK data.

Maximum Concentration (Cmax) of LY3023414 and Necitumumab

Outcome measures

Outcome measures
Measure	Lead in Cohort LY3023414 + Necitumumab n=23 Participants 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.	Post Lead in Cohort LY3023414 + Necitumumab n=26 Participants 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.
Pharmacokinetics: Maximum Concentration (Cmax) of LY3023414 and Necitumumab Cycle 1 Day 8	738 ng/mL Geometric Coefficient of Variation 103	318000 ng/mL Geometric Coefficient of Variation 27
Pharmacokinetics: Maximum Concentration (Cmax) of LY3023414 and Necitumumab Cycle 3 Day 8	1302 ng/mL Geometric Coefficient of Variation 70	345000 ng/mL Geometric Coefficient of Variation 14

Adverse Events

Lead in Cohort LY3023414 + Necitumumab

Serious events: 3 serious events

Other events: 15 other events

Deaths: 11 deaths

Post Lead in Cohort LY3023414 + Necitumumab

Serious events: 5 serious events

Other events: 16 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Lead in Cohort LY3023414 + Necitumumab n=15 participants at risk 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.	Post Lead in Cohort LY3023414 + Necitumumab n=16 participants at risk 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.
Cardiac disorders Atrial fibrillation	6.7% 1/15 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.	0.00% 0/16 • Up To 330 Days All participants who received at least one dose of study drug.
Cardiac disorders Atrial flutter	6.7% 1/15 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.	0.00% 0/16 • Up To 330 Days All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.	0.00% 0/16 • Up To 330 Days All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Infections and infestations Lung infection	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Infections and infestations Pneumonia fungal	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Nervous system disorders Seizure	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.
Vascular disorders Haematoma	6.7% 1/15 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.	0.00% 0/16 • Up To 330 Days All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/15 • Up To 330 Days All participants who received at least one dose of study drug.	6.2% 1/16 • Number of events 1 • Up To 330 Days All participants who received at least one dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60