Trial Outcomes & Findings for Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE) (NCT NCT01684878)

Last Updated: 2017-05-23

Results Overview

An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

208 participants

Primary outcome timeframe

Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

Results posted on

2017-05-23

Participant Flow

A total of 208 participants were entered into the study, 52 participants in Part 1, and 156 participants in Part 2 of the study. Of these, 203 received treatment with pertuzumab or pertuzumab-placebo (50 participants in Part 1 and 153 participants in Part 2).

Participant milestones

Participant milestones
Measure	Part 1: Pertuzumab + Topotecan Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 2: Pertuzumab+Chemotherapy Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Part 2: Placebo+Chemotherapy Participants received pertuzumab-matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Part 1: Safety Run in Phase STARTED	22	28	0	0
Part 1: Safety Run in Phase COMPLETED	6	5	0	0
Part 1: Safety Run in Phase NOT COMPLETED	16	23	0	0
Part 2: Randomized Phase STARTED	0	0	78	78
Part 2: Randomized Phase Participants Randomized But Not Treated	0	0	1	2
Part 2: Randomized Phase Participants Mis-randomized	0	0	2	0
Part 2: Randomized Phase COMPLETED	0	0	0	0
Part 2: Randomized Phase NOT COMPLETED	0	0	78	78

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Pertuzumab + Topotecan Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 2: Pertuzumab+Chemotherapy Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Part 2: Placebo+Chemotherapy Participants received pertuzumab-matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Part 1: Safety Run in Phase Participants withdrawn consent	1	1	0	0
Part 1: Safety Run in Phase Death	15	20	0	0
Part 1: Safety Run in Phase Lost to Follow-up	0	2	0	0
Part 2: Randomized Phase Participant withdrew consent	0	0	1	2
Part 2: Randomized Phase Lost to Follow-up	0	0	2	0
Part 2: Randomized Phase Death	0	0	62	68
Part 2: Randomized Phase Alive at data-cut	0	0	13	7
Part 2: Randomized Phase Participant noncompliance	0	0	0	1

Baseline Characteristics

Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Pertuzumab + Topotecan n=22 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=28 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 2: Pertuzumab+Chemotherapy n=78 Participants Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Part 2: Placebo+Chemotherapy n=78 Participants Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Total n=206 Participants Total of all reporting groups
Age, Customized Less than or equal to (≤)65 years	15 participants n=5 Participants	17 participants n=7 Participants	40 participants n=5 Participants	44 participants n=4 Participants	116 participants n=21 Participants
Age, Customized Greater than (>)65 years	7 participants n=5 Participants	11 participants n=7 Participants	38 participants n=5 Participants	34 participants n=4 Participants	90 participants n=21 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	28 Participants n=7 Participants	78 Participants n=5 Participants	78 Participants n=4 Participants	206 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

Population: All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=22 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=28 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 1: Percentage of Participants With Adverse Events (AEs)	95.5 percentage of participants	100.0 percentage of participants

PRIMARY outcome

Timeframe: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Population: ITT Population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).

PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=78 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=78 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)	4.27 months Interval 3.65 to 6.11	2.74 months Interval 2.14 to 4.73

SECONDARY outcome

Timeframe: Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)

Population: All Treated participants with measurable disease at baseline.

ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=14 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=24 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 1- Objective Response Rate (ORR)	14.3 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Population: ITT population with measurable disease at baseline.

ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=61 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=69 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2- Objective Response Rate (ORR)	14.8 percentage of participants Interval 7.0 to 26.2	8.7 percentage of participants Interval 3.3 to 18.0

SECONDARY outcome

Timeframe: Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)

Population: All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.

PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=22 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=28 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 1: PFS Assessed by the Investigator	4.07 months Interval 1.94 to 6.08	4.24 months Interval 3.45 to 6.01

SECONDARY outcome

Timeframe: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Population: ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)

PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=78 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=78 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2: Progression-free Survival (PFS) Assessed by the Investigator	4.22 months Interval 3.25 to 5.22	3.94 months Interval 2.63 to 4.3

SECONDARY outcome

Timeframe: Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)

Population: ITT population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=78 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=78 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Functional Scales: Physical (n=71, 74)	71.1 units on a scale Standard Deviation 22.77	74.9 units on a scale Standard Deviation 20.85
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Functional Scales: Role (n=70, 73)	68.6 units on a scale Standard Deviation 33.16	69.4 units on a scale Standard Deviation 32.40
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Functional Scales: Emotional (n=71, 73)	59.5 units on a scale Standard Deviation 24.03	65.9 units on a scale Standard Deviation 23.42
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Functional Scales: Cognitive (n=71, 73)	81.2 units on a scale Standard Deviation 25.34	84.9 units on a scale Standard Deviation 20.25
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Functional Scales: Social (n=71, 73)	70.7 units on a scale Standard Deviation 30.01	68.3 units on a scale Standard Deviation 29.81
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Fatigue (n=71, 74)	41.2 units on a scale Standard Deviation 28.75	38.4 units on a scale Standard Deviation 27.77
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Nausea and vomiting (n=72, 74)	10.4 units on a scale Standard Deviation 15.68	12.4 units on a scale Standard Deviation 20.47
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Pain (n=72, 74)	35.2 units on a scale Standard Deviation 31.34	31.1 units on a scale Standard Deviation 29.24
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Dyspnoea (n=68, 73)	22.5 units on a scale Standard Deviation 28.47	21.5 units on a scale Standard Deviation 27.98
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Insomnia (n=69, 74)	35.3 units on a scale Standard Deviation 31.25	31.5 units on a scale Standard Deviation 31.16
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Appetite loss (n=71, 73)	24.9 units on a scale Standard Deviation 30.19	21.0 units on a scale Standard Deviation 26.36
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Constipation (n=69, 72)	25.6 units on a scale Standard Deviation 32.41	26.4 units on a scale Standard Deviation 32.59
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales: Diarrhoea (n=69, 72)	14.5 units on a scale Standard Deviation 26.49	14.4 units on a scale Standard Deviation 22.26
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Symptomatic Scales:Financial difficulties(n=70,72	17.6 units on a scale Standard Deviation 28.78	13.4 units on a scale Standard Deviation 22.83
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score Global health status / QoL scale (n=71, 72)	54.1 units on a scale Standard Deviation 24.99	61.1 units on a scale Standard Deviation 22.29

SECONDARY outcome

Timeframe: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

Population: Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=77 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=76 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2: Percentage of Participants With Adverse Events (AEs)	98.7 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Population: ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)

Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause

Outcome measures

Outcome measures
Measure	Part 1: Pertuzumab + Topotecan n=78 Participants Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Part 1: Pertuzumab + Paclitaxel n=78 Participants Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Part 2: Overall Survival	10.18 months Interval 6.67 to 15.24	8.36 months Interval 6.14 to 11.99

Adverse Events

Part 1: Pertuzumab + Topotecan

Serious events: 9 serious events

Other events: 21 other events

Deaths: 0 deaths

Part 1: Pertuzumab + Paclitaxel

Serious events: 11 serious events

Other events: 27 other events

Deaths: 0 deaths

Part 2: Pertuzumab+Chemotherapy

Serious events: 29 serious events

Other events: 72 other events

Deaths: 0 deaths

Part 2: Placebo+Chemotherapy

Serious events: 33 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

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