Trial Outcomes & Findings for A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC). (NCT NCT00760929)

Last Updated: 2021-01-05

Results Overview

PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants who had not died or progressed at the time of the final analysis were censored at the date of last contact.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

171 participants

Primary outcome timeframe

12 weeks

Results posted on

2021-01-05

Participant Flow

A screening examination was to be performed between -28 and 1 days before first day of treatment.

Safety population was used for the participant flow. All randomized participants who received at least one treatment. Two patients randomized to placebo QW actually received R1507 9 mg/kg QW.

Participant milestones

Participant milestones
Measure	Placebo for R1507 (9mg/kg iv) Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.	Placebo for R1507 (16mg/kg iv) Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Overall Study STARTED	26	29	59	57
Overall Study COMPLETED	0	1	1	2
Overall Study NOT COMPLETED	26	28	58	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo for R1507 (9mg/kg iv) Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.	Placebo for R1507 (16mg/kg iv) Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Overall Study Adverse Event	2	0	6	10
Overall Study Lack of Efficacy	0	2	1	0
Overall Study Withdrawal by Subject	1	0	9	1
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Progression of Disease	21	26	38	42
Overall Study Other	2	0	2	1
Overall Study Death	0	0	1	0
Overall Study Violation of Selection Criteria at Entry	0	0	0	1

Baseline Characteristics

A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo for R1507 (9mg/kg iv) n=26 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.	Placebo for R1507 (16mg/kg iv) n=29 Participants Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=59 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=57 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Total n=171 Participants Total of all reporting groups
Age, Continuous	62.0 Years STANDARD_DEVIATION 8.01 • n=5 Participants	62.3 Years STANDARD_DEVIATION 8.26 • n=7 Participants	60.3 Years STANDARD_DEVIATION 10.45 • n=5 Participants	60.5 Years STANDARD_DEVIATION 9.82 • n=4 Participants	61.0 Years STANDARD_DEVIATION 9.56 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants	19 Participants n=4 Participants	57 Participants n=21 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants	38 Participants n=4 Participants	114 Participants n=21 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized White	26 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants	56 Participants n=4 Participants	166 Participants n=21 Participants
Smoking Status Current smoker	3 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	22 Participants n=21 Participants
Smoking Status Never smoked	3 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	20 Participants n=21 Participants
Smoking Status Past smoker	20 Participants n=5 Participants	19 Participants n=7 Participants	45 Participants n=5 Participants	45 Participants n=4 Participants	129 Participants n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=57 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=57 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Number of Participants With Progression Free Survival (PFS) Progression-Free & Alive	18 Participants	16 Participants	21 Participants
Number of Participants With Progression Free Survival (PFS) Progressed, Died, or Unknown	39 Participants	41 Participants	36 Participants

SECONDARY outcome

Timeframe: From baseline up to 20 months

OS was defined as the median time, in weeks, from the date of randomization to the date of death, due to any cause. Participants who have not died at the time of the final analysis will be censored at the date the participant was last known to be alive. The 90% CI was estimated using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=57 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=57 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Overall Survival (OS)	35.1 Weeks Interval 20.9 to 44.7	35.1 Weeks Interval 26.1 to 43.4	52.4 Weeks Interval 33.7 to 65.7

SECONDARY outcome

Timeframe: From baseline up to 20 months

Objective response rate (ORR) was defined by RECIST criteria as the best response achieved by a patient over the course of the trial, which includes a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation, stable disease (SD), or progressive disease (PD). PR was defined as ≥ 30% decrease in sum of longest diameter of all target lesions, from baseline sum. CR was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. PD = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=57 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=57 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Objective Response Rate	8.8 Percentage of Participants Interval 3.5 to 17.6	7 Percentage of Participants Interval 2.4 to 15.3	7 Percentage of Participants Interval 2.4 to 15.3

SECONDARY outcome

Timeframe: From baseline up to 20 months

Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=4 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=4 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Duration of Response	260.40 days Standard Deviation 140.56	215.50 days Standard Deviation 91.70	257.75 days Standard Deviation 130.07

SECONDARY outcome

Timeframe: From baseline up to 20 months

This is defined for participants with objective response, as the date of randomization to the date of first CR or PR which will be the date the response is first radiographically documented following initiation of therapy (the date of the actual imaging modality).

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	R1507 (9mg/kg iv) n=4 Participants Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	R1507 (16mg/kg iv) n=4 Participants Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Time to Response	42.40 days Standard Deviation 4.34	65.25 days Standard Deviation 22.95	85.25 days Standard Deviation 34.70

Adverse Events

Placebo for R1507 (9mg/kg iv)

Serious events: 5 serious events

Other events: 26 other events

Deaths: 20 deaths

Placebo for R1507 (16mg/kg iv)

Serious events: 3 serious events

Other events: 27 other events

Deaths: 22 deaths

R1507 (9mg/kg iv)

Serious events: 18 serious events

Other events: 57 other events

Deaths: 43 deaths

R1507 (16mg/kg iv)

Serious events: 14 serious events

Other events: 56 other events

Deaths: 34 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER