A Phase 3 interventional study of avelumab and PLD in Ovarian Cancer, sponsored by Pfizer. Completed at 296 sites in 25 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-10.
Sponsored by Pfizer · Phase 3, Interventional, and Treatment
A Phase 3 global study comparing avelumab alone to avelumab plus PLD and to PLD alone to demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Overall Survival in patients with platinum resistant/platinum refractory ovarian cancer.
2,695 studies on the registry are indexed under Ovarian Neoplasms; 727 are open to participants now.
This study's enrollment of 566 is above the median of 60 across 2,030 interventional studies indexed under Ovarian Neoplasms.
Browse Ovarian Neoplasms studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Mandatory tumor biopsy must be performed prior to enrollment for all patients (unless there is a documented clinical contraindication). In addition, availability of archived FFPE tumor tissue should be confirmed. If a patient underwent tumor tissue collection within 3 months prior to enrollment with no intervening treatment, and the sample is provided, then a new de novo tumor biopsy is not required.
Exclusion Criteria:
Arm A: avelumab alone
Biological: avelumab
Arm B: avelumab plus PLD
Biological: avelumab · Drug: PLD
Arm C: PLD alone
Drug: PLD
10 mg/kg will be given as a 1 hour intravenous infusion (IV) every 2 weeks (Q2W) in 4 week cycles
PLD (Arm B, Arm C) 40 mg/m2 will be given as a 1 hour IV infusion every 4 weeks (Q4W) in 4 week cycles
Also known as: doxorubicin, caelyx
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.
Time frame: From randomization until the date of first documented progression or date of deaths from any cause, whichever came first, assessed up to 30 months (based on cutoff date: 19 September 2018).
Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.
Time frame: From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.
Objective Response Rate (ORR) Based on BICR Assessment
Percentage of participants achieved objective response (OR) based on BICR assessment is presented for this endpoint. OR is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, \>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met and before the first documentation of disease progression. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.
Time frame: Tumor assessments as assessed by BICR were conducted at every 8 weeks from screening until documented disease progression (approximately up to 30 months); based on cutoff date: 19 September 2018.
ORR Based on Investigator Assessment
Percentage of participants achieved OR based on investigator assessment is presented for this endpoint. OR is defined as a CR (disappearance of all target lesions) or PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. The ORR on each randomized treatment arm were estimated by dividing the number of participants with OR (CR or PR) by number of participants randomized to the respective treatment arm.
Time frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.
PFS Based on Investigator Assessment According to RECIST Version 1.1
PFS is defined as the time from date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method.
Time frame: From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.
Duration of Response (DR) Based on BICR Assessment
DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Time frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.
DR Based on Investigator Assessment
DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Time frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.
Disease Control (DC) Rate Based on BICR Assessment
Percentage of participants achieving DC based on BICR assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or stable disease (SD) according to the RECIST version 1.1.
Time frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.
DC Rate Based on Investigator Assessment
Percentage of participants achieving DC based on investigator assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or SD according to the RECIST version 1.1.
Time frame: Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; progression of the malignancy under study. Treatment emergent AEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.
Time frame: From the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months); based on cutoff date: 13 July 2022.
Number of Participants With Laboratory Abnormalities
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 4.03 were summarized: hematology (anemia, lymphocyte count decreased, neutrophil count decreased; and platelet count decreased) and chemistry laboratory tests (creatinine increased; serum amylase increased and lipase increased).
Time frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.
Change From Baseline in Vital Signs - Blood Pressure
Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.
Time frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.
Change From Baseline in Vital Signs - Pulse Rate
Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
Time frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.
Number of Participants With Electrocardiogram (ECG) Abnormalities
Categorical summarization ECG criteria were as follows: 1) QT interval, QTcB, QTcF and QTcP: increase from baseline \>30 ms or 60 ms; absolute value \> 450 ms, \>480 ms and \> 500 ms; 2) heart rate (HR): change from baseline \>=20 bpm and absolute value \<=50 bpm or \>=120 bpm; 3) PR interval: absolute value \>=220 ms and increase from baseline \>=20 ms; 4) QRS: \>= 120 ms.
Time frame: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.
Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline
LVEF decrease was summarized by multiple-gated acquisition (MUGA)/ echocardiogram (ECHO) parameter. Participants with a LVEF% \>=10 points and \>= 15 points decrease from baseline during the on-treatment period were summarized.
Time frame: Screening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.
Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS
PD-L1 expression was assessed by immunohistochemistry. Participants were considered positive for PD-L1 if their baseline tissue sample demonstrated PD-L1 expression on \>=1% of tumor cells or \>=5% of immune cells.
Time frame: Biomarkers are measured only at screening.
Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS
Tumor infiltrating CD8 positive (CD8+) T lymphocytes was assessed by immunohistochemistry. Participants were considered positive for CD8 T cells if their baseline tissue sample demonstrated presence of \>=1% CD8+ cells across the area of the tumor.
Time frame: Biomarkers are measured only at screening.
Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) is a 30 question survey and includes 5 functional domain subscales, global health status/quality of life, disease/treatment related symptoms, and the perceived financial impact of disease. Higher scores are reflective of a greater presence of symptoms.
Time frame: Day 1 of Cycle 1, Day 1 of each subsequent cycle, end of treatment/withdrawal visit and the 30, 60 and 90 days safety follow up visits, based on cutoff date: 19 September 2018.
Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28 item instrument with 7 functional domain subscales. Time to deterioration was defined as the time from randomization to the first time the participant's score showed a 15-point or higher increase in the score of the abdominal/GI symptom subscale of the EORTC QLQ-OV28.
Time frame: From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.
Change From Baseline in EQ-VAS Score at End of Treatment
The EuroQol- 5 Dimensions- 5 Levels (EQ-5D-5L) questionnaire consists of the EQ-5D-5L descriptive system and a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.
Time frame: Baseline and end of treatment/withdrawal visit
Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) Dose
Ctrough was defined as predose concentration during multiple dosing, and can be observed directly from data.
Time frame: At predose (0 H) on Cycle 2 Day 1
Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD Dose
Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
Time frame: At postdose (end of infusion, 1H) on Cycle 2 Day 1
Cmax For Doxorubicin Following Cycle 2 Day 1 PLD Dose
Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
Time frame: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose
Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
AUC24 was defined as area under the concentration time profile from time zero to 24 hours.
Time frame: From 0 through 24 hours postdose
Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
AUC336 was defined as area under the concentration time profile from time zero to 336 hours.
Time frame: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose
Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
AUClast was defined as area under the concentration time profile from time zero to the time of the last quantifiable concentration (Clast).
Time frame: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose
Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA)
Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab.
Time frame: At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab
Number of Participants With Treatment-Induced ADA
Treatment-induced ADA was defined as participant who was ADA-negative at baseline and has at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
Time frame: At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab
Number of Participants With Treatment-Induced Neutralizing Antibody (nAb)
Treatment-induced nAb was defined as participant who was not nAb positive at baseline and had at least one positive post-baseline nAb result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
Time frame: At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab
| Milestone | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Started | 188 | 188 | 190 |
| Treated | 187 | 182 | 177 |
| Completed | 0 | 0 | 0 |
| Not completed | 188 | 188 | 190 |
| Withdrew: Adverse event | 16 | 30 | 20 |
| Withdrew: Death | 4 | 4 | 5 |
| Withdrew: Physician decision | 1 | 3 | 11 |
| Withdrew: Other | 5 | 1 | 3 |
| Withdrew: Withdrawal by subject | 4 | 7 | 31 |
| Withdrew: Global deterioration of health status | 19 | 18 | 24 |
| Withdrew: No longer meets eligibility criteria | 1 | 0 | 2 |
| Withdrew: Progressive disease | 137 | 125 | 94 |
| Withdrew: Non-compliance with study drug | 1 | 0 | 0 |
OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.
| months | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Overall Survival (OS) | 11.8 (8.9 to 14.1) | 15.7 (12.7 to 18.7) | 13.1 (11.8 to 15.5) |
PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.
| months | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 1.9 (1.8 to 1.9) | 3.7 (3.3 to 5.1) | 3.5 (2.1 to 4.0) |
Percentage of participants achieved objective response (OR) based on BICR assessment is presented for this endpoint. OR is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, \>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met and before the first documentation of disease progression. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.
| percentage of participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Objective Response Rate (ORR) Based on BICR Assessment | 3.7 (1.5 to 7.5) | 13.3 (8.8 to 19.0) | 4.2 (1.8 to 8.1) |
Percentage of participants achieved OR based on investigator assessment is presented for this endpoint. OR is defined as a CR (disappearance of all target lesions) or PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. The ORR on each randomized treatment arm were estimated by dividing the number of participants with OR (CR or PR) by number of participants randomized to the respective treatment arm.
| percentage of participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| ORR Based on Investigator Assessment | 5.3 (2.6 to 9.6) | 18.6 (13.3 to 24.9) | 9.5 (5.7 to 14.6) |
PFS is defined as the time from date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method.
| month | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| PFS Based on Investigator Assessment According to RECIST Version 1.1 | 1.9 (1.8 to 1.9) | 4.7 (3.7 to 6.0) | 3.7 (3.5 to 5.4) |
DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
| months | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Duration of Response (DR) Based on BICR Assessment | 9.2 (6.4 to NA) | 8.5 (6.1 to NA) | 13.1 (5.5 to NA) |
DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
| months | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| DR Based on Investigator Assessment | 10.4 (3.7 to NA) | 7.6 (5.6 to 9.1) | 7.4 (3.6 to 11.2) |
Percentage of participants achieving DC based on BICR assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or stable disease (SD) according to the RECIST version 1.1.
| percentage of participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Disease Control (DC) Rate Based on BICR Assessment | 33.0 (26.3 to 40.2) | 57.4 (50.0 to 64.6) | 48.9 (41.6 to 56.3) |
Percentage of participants achieving DC based on investigator assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or SD according to the RECIST version 1.1.
| percentage of participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| DC Rate Based on Investigator Assessment | 34.0 (27.3 to 41.3) | 61.7 (54.3 to 68.7) | 54.7 (47.4 to 62.0) |
An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; progression of the malignancy under study. Treatment emergent AEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| TEAE | 180 | 180 | 173 |
| Treatment emergent SAEs | 72 | 74 | 51 |
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 4.03 were summarized: hematology (anemia, lymphocyte count decreased, neutrophil count decreased; and platelet count decreased) and chemistry laboratory tests (creatinine increased; serum amylase increased and lipase increased).
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Anemia | 135 | 155 | 144 |
| Lymphocyte count decreased | 89 | 148 | 107 |
| Neutrophil count decreased | 26 | 80 | 62 |
| Platelet count decreased | 33 | 48 | 50 |
| Creatinine increased | 154 | 151 | 120 |
| Serum amylase increased | 43 | 35 | 27 |
| Lipase increased | 27 | 33 | 21 |
Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.
| mm Hg | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| DBP Cycle 1 Day 15 | 0.1 ± 9.79 | -2.2 ± 9.12 | 0.7 ± 8.89 |
| DBP Cycle 2 Day 1 | -1.1 ± 9.61 | -2.8 ± 8.01 | -0.1 ± 9.34 |
| DBP Cycle 2 Day 15 | 0.1 ± 10.05 | -2.8 ± 9.19 | -0.1 ± 8.83 |
| DBP Cycle 3 Day 1 | 0 ± 10.81 | -2.7 ± 8.95 | -0.2 ± 8.96 |
| DBP Cycle 3 Day 15 | -0.6 ± 9.25 | -2.3 ± 8.56 | -0.5 ± 8.67 |
| DBP End of Treatment | 1.1 ± 10.87 | -0.3 ± 11.08 | 0.8 ± 10.40 |
| SBP Cycle 1 Day 15 | -0.9 ± 14.35 | -2.3 ± 13.12 | -1.0 ± 13.94 |
| SBP Cycle 2 Day 1 | -2.2 ± 14.44 | -3.4 ± 13.70 | -2.8 ± 13.39 |
| SBP Cycle 2 Day 15 | -0.6 ± 14.11 | -3.7 ± 14.78 | -1.8 ± 14.98 |
| SBP Cycle 3 Day 1 | -0.2 ± 15.59 | -2.7 ± 14.36 | -1.5 ± 14.14 |
| SBP Cycle 3 Day 15 | -0.2 ± 13.78 | -2.1 ± 15.30 | -2.2 ± 13.96 |
| SBP End of Treatment | -0.9 ± 17.21 | -1.0 ± 16.83 | -3.2 ± 15.92 |
Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
| bpm | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Cycle 1 Day 15 | 2.9 ± 9.95 | 1.8 ± 12.10 | 3.5 ± 10.70 |
| Cycle 2 Day 1 | 2.6 ± 10.92 | 2.9 ± 11.18 | 1.7 ± 9.71 |
| Cycle 2 Day 15 | 2.9 ± 11.19 | 3.5 ± 11.79 | 3.2 ± 11.54 |
| Cycle 3 Day 1 | 2.4 ± 10.00 | 2.1 ± 11.78 | 1.4 ± 11.14 |
| Cycle 3 Day 15 | 3.0 ± 12.23 | 1.4 ± 11.44 | 2.4 ± 10.41 |
| End of Treatment | 7.7 ± 14.27 | 7.4 ± 13.70 | 5.7 ± 14.10 |
Categorical summarization ECG criteria were as follows: 1) QT interval, QTcB, QTcF and QTcP: increase from baseline \>30 ms or 60 ms; absolute value \> 450 ms, \>480 ms and \> 500 ms; 2) heart rate (HR): change from baseline \>=20 bpm and absolute value \<=50 bpm or \>=120 bpm; 3) PR interval: absolute value \>=220 ms and increase from baseline \>=20 ms; 4) QRS: \>= 120 ms.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| QT increase from baseline >30 ms | 26 | 40 | 47 |
| QT increase from baseline >60 ms | 5 | 9 | 4 |
| QT >450 ms | 6 | 10 | 5 |
| QT >480 ms | 1 | 2 | 2 |
| QT >500 ms | 1 | 1 | 1 |
| QTcB increase from baseline >30 ms | 33 | 36 | 22 |
| QTcB increase from baseline >60 ms | 9 | 7 | 8 |
| QTcB >450 ms | 56 | 63 | 45 |
| QTcB >480 ms | 9 | 19 | 9 |
| QTcB >500 ms | 5 | 9 | 5 |
| QTcF increase from baseline >30 ms | 19 | 24 | 13 |
| QTcF increase from baseline >60 ms | 6 | 5 | 5 |
| QTcF >450 ms | 18 | 27 | 14 |
| QTcF >480 ms | 4 | 8 | 5 |
| QTcF >500 ms | 3 | 2 | 4 |
| QTcP increase from baseline >30 ms | 17 | 23 | 12 |
| QTcP increase from baseline >60 ms | 6 | 5 | 4 |
| QTcP >450 ms | 19 | 29 | 17 |
| QTcP >480 ms | 2 | 7 | 2 |
| QTcP >500 ms | 1 | 2 | 2 |
| Heart rate <=50 bpm and decrease >= 20 bpm | 0 | 1 | 0 |
| Heart rate >=120 bpm and increase >= 20 bpm | 5 | 5 | 3 |
| PR >=220 ms and increase from baseline >=20 ms | 3 | 4 | 2 |
| QRS >=120 ms | 7 | 9 | 9 |
LVEF decrease was summarized by multiple-gated acquisition (MUGA)/ echocardiogram (ECHO) parameter. Participants with a LVEF% \>=10 points and \>= 15 points decrease from baseline during the on-treatment period were summarized.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| >= 10 point decrease from baseline | 8 | 22 | 13 |
| >= 15 point decrease from baseline | 3 | 8 | 3 |
PD-L1 expression was assessed by immunohistochemistry. Participants were considered positive for PD-L1 if their baseline tissue sample demonstrated PD-L1 expression on \>=1% of tumor cells or \>=5% of immune cells.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS | 100 | 100 | 88 |
Tumor infiltrating CD8 positive (CD8+) T lymphocytes was assessed by immunohistochemistry. Participants were considered positive for CD8 T cells if their baseline tissue sample demonstrated presence of \>=1% CD8+ cells across the area of the tumor.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS | 76 | 80 | 72 |
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) is a 30 question survey and includes 5 functional domain subscales, global health status/quality of life, disease/treatment related symptoms, and the perceived financial impact of disease. Higher scores are reflective of a greater presence of symptoms.
| Participants | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Deterioration | 46 | 65 | 46 |
| Improved | 23 | 20 | 26 |
| Stable | 83 | 81 | 76 |
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28 item instrument with 7 functional domain subscales. Time to deterioration was defined as the time from randomization to the first time the participant's score showed a 15-point or higher increase in the score of the abdominal/GI symptom subscale of the EORTC QLQ-OV28.
| months | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28 | NA (NA to NA) | 11.1 (6.5 to NA) | 10.6 (9.2 to NA) |
The EuroQol- 5 Dimensions- 5 Levels (EQ-5D-5L) questionnaire consists of the EQ-5D-5L descriptive system and a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.
| scores on a scale | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Change From Baseline in EQ-VAS Score at End of Treatment | -13.6 ± 20.56 | -11.2 ± 19.79 | -7.7 ± 22.26 |
Ctrough was defined as predose concentration during multiple dosing, and can be observed directly from data.
| microgram per milliliter (mcg/mL) | Avelumab | Avelumab + PLD |
|---|---|---|
| Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) Dose | 21.1 ± 89 | 23.19 ± 74 |
Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
| mcg/mL | Avelumab | Avelumab + PLD |
|---|---|---|
| Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD Dose | 231.6 ± 43 | 207.9 ± 71 |
Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
| nanogram per milliliter (ng/mL) | Pegylated Liposomal Doxorubicin (PLD) | Avelumab + PLD |
|---|---|---|
| Cmax For Doxorubicin Following Cycle 2 Day 1 PLD Dose | 26810 ± 14 | 25850 ± 17 |
AUC24 was defined as area under the concentration time profile from time zero to 24 hours.
| nanogram*hour per milliliter (ng*hr/mL) | Pegylated Liposomal Doxorubicin (PLD) | Avelumab + PLD |
|---|---|---|
| Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD Dose | 567600 ± 11 | 541700 ± 14 |
AUC336 was defined as area under the concentration time profile from time zero to 336 hours.
| ng*hr/mL | Pegylated Liposomal Doxorubicin (PLD) | Avelumab + PLD |
|---|---|---|
| Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD Dose | 2848000 ± 20 | 2571000 ± 30 |
AUClast was defined as area under the concentration time profile from time zero to the time of the last quantifiable concentration (Clast).
| ng*hr/mL | Pegylated Liposomal Doxorubicin (PLD) | Avelumab + PLD |
|---|---|---|
| Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD Dose | 2043000 ± 119 | 2052000 ± 71 |
Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab.
| Participants | Avelumab | Avelumab + PLD | All Participants |
|---|---|---|---|
| Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA) | 1 | 0 | 1 |
Treatment-induced ADA was defined as participant who was ADA-negative at baseline and has at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
| Participants | Avelumab | Avelumab + PLD | All Participants |
|---|---|---|---|
| Number of Participants With Treatment-Induced ADA | 27 | 2 | 29 |
Treatment-induced nAb was defined as participant who was not nAb positive at baseline and had at least one positive post-baseline nAb result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
| Participants | Avelumab | Avelumab + PLD | All Participants |
|---|---|---|---|
| Number of Participants With Treatment-Induced Neutralizing Antibody (nAb) | 5 | 1 | 6 |
Collected over AEs (serious and non-serious) should be reported from the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months). Based on the cutoff: 13 July 2022.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Avelumab | 122/187 (65.2%) | 72/187 (38.5%) | 173/187 (92.5%) |
| Avelumab + PLD | 107/182 (58.8%) | 74/182 (40.7%) | 176/182 (96.7%) |
| Pegylated Liposomal Doxorubicin (PLD) | 116/177 (65.5%) | 51/177 (28.8%) | 167/177 (94.4%) |
| Event | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| Intestinal obstructionGastrointestinal disorders | 11/187 | 9/182 | 6/177 |
| Disease progressionGeneral disorders | 10/187 | 5/182 | 2/177 |
| Abdominal painGastrointestinal disorders | 9/187 | 6/182 | 6/177 |
| PyrexiaGeneral disorders | 7/187 | 8/182 | 1/177 |
| NauseaGastrointestinal disorders | 7/187 | 4/182 | 1/177 |
| VomitingGastrointestinal disorders | 7/187 | 4/182 | 3/177 |
| ConstipationGastrointestinal disorders | 2/187 | 5/182 | 1/177 |
| HypercalcaemiaMetabolism and nutrition disorders | 0/187 | 5/182 | 1/177 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 3/187 | 5/182 | 0/177 |
| Small intestinal obstructionGastrointestinal disorders | 5/187 | 4/182 | 2/177 |
| Event | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) |
|---|---|---|---|
| NauseaGastrointestinal disorders | 53/187 | 87/182 | 76/177 |
| FatigueGeneral disorders | 63/187 | 77/182 | 55/177 |
| Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders | 1/187 | 61/182 | 40/177 |
| AnaemiaBlood and lymphatic system disorders | 32/187 | 56/182 | 42/177 |
| StomatitisGastrointestinal disorders | 8/187 | 53/182 | 35/177 |
| Abdominal painGastrointestinal disorders | 54/187 | 47/182 | 38/177 |
| Decreased appetiteMetabolism and nutrition disorders | 36/187 | 51/182 | 37/177 |
| RashSkin and subcutaneous tissue disorders | 12/187 | 51/182 | 21/177 |
| ConstipationGastrointestinal disorders | 35/187 | 48/182 | 46/177 |
| VomitingGastrointestinal disorders | 43/187 | 43/182 | 44/177 |
| Age, Categorical(Participants) | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 111 | 124 | 114 | 349 |
| >=65 years | 77 | 64 | 76 | 217 |
| Age, Continuous(years) | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) | Total |
|---|---|---|---|---|
| Mean | 61.0 ± 10.26 | 59.5 ± 10.05 | 60.4 ± 10.64 | 60.3 ± 10.32 |
| Sex: Female, Male(Participants) | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) | Total |
|---|---|---|---|---|
| Female | 188 | 188 | 190 | 566 |
| Male | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 2 | 3 | 1 | 6 |
| Not Hispanic or Latino | 176 | 176 | 183 | 535 |
| Unknown or Not Reported | 10 | 9 | 6 | 25 |
| Race/Ethnicity, Customized(Participants) | Avelumab | Avelumab + PLD | Pegylated Liposomal Doxorubicin (PLD) | Total |
|---|---|---|---|---|
| Race — Black or African American | 2 | 2 | 6 | 10 |
| Race — American Indian or Alaska Native | 0 | 0 | 1 | 1 |
| Race — Asian | 34 | 53 | 46 | 133 |
| Race — Native Hawaiian or Other Pacific Islander | 1 | 0 | 0 | 1 |
| Race — White | 148 | 133 | 135 | 416 |
| Race — Other | 1 | 0 | 2 | 3 |
| Race — Unknown | 2 | 0 | 0 | 2 |
Showing the first 100 of 296 sites across 25 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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