M18-007

OncoMed Pharmaceuticals, Inc

800 Chesapeake Drive, Redwood City, United States, CA 94063

Senior Vice President Clinical Research Robert Stagg, Pharm. D., OncoMed Pharmaceuticals, Inc., 1 650-995-8200, bob.stagg@oncomed.com

Senior Vice President Clinical Research Robert Stagg, Pharm. D., OncoMed Pharmaceuticals, Inc., 1 650-995-8200, bob.stagg@oncomed.com

No

No

No

Final

31 Aug 2017

Yes

07 Apr 2017

Yes

07 Apr 2017

No

To compare the efficacy of Arm 1 to Arm 2 and Arm 1 to Arm 3 in subjects with 1st-line stage IV non-squamous non-small cell lung cancer

In the absence of unacceptable toxicities or disease progression per RECIST v1.1, subjects continued to receive study treatment. Regardless of discontinuation of one, two, or all three study drugs, subjects could continue on study with assessments. Once discontinuation criteria for the study were met (disease progression, use of other anticancer therapy, subject or investigator decision or protocol non-compliance), a termination visit occurred ≤14 days later. Subjects who did not meet the criteria to receive the second 4-cycle course of placebo or demcizumab continued to receive maintenance pemetrexed per protocol without demcizumab or placebo. To reduce gastrointestinal and hematologic toxicity, subjects received oral folic acid of ≥400 μg daily for at least 5 of the 7 days preceding the first dose of pemetrexed and continued daily during the full course of therapy and for 21 days after the last dose of pemetrexed. Subjects also received an intramuscular injection of vitamin B12 1000 μg during the week preceding the first dose of pemetrexed and then every 63 days while being treated with pemetrexed. Unless contraindicated, subjects also received dexamethasone 4 mg orally twice daily on the day before, the day of, and the day after pemetrexed administration to reduce the risk of developing skin rash.

03 Feb 2015

No

No

Spain: 20

Belgium: 2

Italy: 7

Australia: 33

United States: 20

82

29

0

0

0

0

0

0

49

33

0

Treatment Period (overall period)

Randomised - controlled

Yes

Placebo

Solution for infusion

Intravenous use

A necessary amount placebo was withdrawn to obtain the required dose and diluted with 5% dextrose in water, USP, to a total volume of 250 ml. Placebo was a clear to slightly opalescent, colorless to slightly yellow, liquid formulation of 50 mM histidine, 100 mM sodium chloride, 45 mM sucrose, and 0.01% (v/v) polysorbate-20, pH 6.0. Placebo was administered first, followed by pemetrexed, and then carboplatin immediately afterwards.

Placebo

Solution for infusion

Intravenous use

A necessary amount placebo was withdrawn to obtain the required dose and diluted with 5% dextrose in water, USP, to a total volume of 250 ml. Placebo was a clear to slightly opalescent, colorless to slightly yellow, liquid formulation of 50 mM histidine, 100 mM sodium chloride, 45 mM sucrose, and 0.01% (v/v) polysorbate-20, pH 6.0. Placebo was administered first, followed by pemetrexed, and then carboplatin immediately afterwards.

Demcizumab

Concentrate for solution for infusion

Intravenous use

Demcizumab was supplied at a concentration of 10 mg/mL in a 25-mL single-use glass vial filled to 20 mL to deliver a total of 200 mg per vial. Demcizumab and placebo vials were to be refrigerated at 2°C to 8°C. Demcizumab and placebo were not to be shaken or frozen. Demcizumab 5 mg/kg or placebo was administered once every 3 weeks for 4 cycles (i.e., the last administration on Day 63). A second course of Demcizumab 5 mg/kg or placebo was administered once every 3 weeks for 63 days starting at Day 168 only if they met the original cardiac-related eligibility criteria (see exclusion criterion 21), they did not develop pulmonary hypertension or heart failure while on study, and blood pressure was controlled to ≤140/90 mm Hg.

Demcizumab

Concentrate for solution for infusion

Intravenous use

Demcizumab was supplied at a concentration of 10 mg/mL in a 25-mL single-use glass vial filled to 20 mL to deliver a total of 200 mg per vial. Demcizumab and placebo vials were to be refrigerated at 2°C to 8°C. Demcizumab and placebo were not to be shaken or frozen. Demcizumab 5 mg/kg or placebo was administered once every 3 weeks for 4 cycles (i.e., the last administration on Day 63). A second course of Demcizumab 5 mg/kg or placebo was administered once every 3 weeks for 63 days starting at Day 168 only if they met the original cardiac-related eligibility criteria (see exclusion criterion 21), they did not develop pulmonary hypertension or heart failure while on study, and blood pressure was controlled to ≤140/90 mm Hg.

Placebo/placebo arm (Arm 1)

Demcizumab/placebo arm (Arm 2)

Demcizumab/demcizumab arm (Arm 3)

Intent-to-treat (ITT) Population

The ITT Population comprised all subjects who were randomized. Subjects were analyzed as they were randomized.

Per-protocol (PP) Population

The PP population comprised all subjects who received at least 1 dose of demcizumab or placebo and had at least 1 postbaseline tumor assessment. Subjects were analyzed as they were treated. Efficacy, immunogenicity, and biomarker data was analyzed using the PP population as well as the ITT population.

Placebo/placebo arm (Arm 1)

Demcizumab/placebo arm (Arm 2)

Demcizumab/demcizumab arm (Arm 3)

Intent-to-treat (ITT) Population

The ITT Population comprised all subjects who were randomized. Subjects were analyzed as they were randomized.

Per-protocol (PP) Population

The PP population comprised all subjects who received at least 1 dose of demcizumab or placebo and had at least 1 postbaseline tumor assessment. Subjects were analyzed as they were treated. Efficacy, immunogenicity, and biomarker data was analyzed using the PP population as well as the ITT population.

To compare the Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to Demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line Stage IV NSCLC. The primary endpoint of response rate was based on Investigator-assessed BOR and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR, SD, progressive disease (PD), not evaluable, or missing. The number and percentage of subjects in each disease response category (CR, PR, SD, PD, not evaluable, and missing) were summarized by treatment arm.

Primary

The time point of when a subject had progressed (censor = 0) their time to progression was determined by the date of progression (date of RECIST response assessment or date of death) minus start date + 1.

The Kaplan-Meier method was used to estimate both the survival curves and the median survival time. The 95% CI for the median survival time was calculated. A p-value for treatment effect was generated using a stratified Cox proportional hazards model.

Demcizumab/placebo arm (Arm 2) v Demcizumab/demcizumab arm (Arm 3) v Placebo/placebo arm (Arm 1)

82

Pre-specified

0.4

2-sided

All safety analyses were conducted on the safety population. Baseline for safety analysis was the last assessment prior to treatment.

All reported AEs were mapped to standard MedDRA coding terms, grouped by system organ class (SOC) and preferred term (PT) and tabulated by treatment arm.

17.0

Placebo/placebo arm (Arm 1)

Demcizumab/placebo arm (Arm 2)

Demcizumab/demcizumab arm (Arm 3)