Pegylated liposomal doxorubicin (PLD), a type of chemotherapy, is a standard treatment option for patients with platinum-resistant ovarian cancer. However, despite being consider a standard treatment option, the clinical benefit of chemotherapy alone for these patients is small. Historically, response rates for PLD monotherapy have only ranged from 12 to 35% with a high likelihood of recurrence within months after treatment initiation. Although bevacizumab (BEV), an anti-new-vascular growth monoclonal antibody has been approved by FDA to combine with standard chemotherapy (e.g., PLD) for platinum-resistant recurrent ovarian cancer, there are still many restrictions or contraindications preventing certain women from receiving bevacizumab's combination treatment. The goal of this study is to improve upon the activity of PLD in a safe manner to provide a more effective therapeutic option for this group of patients. The purpose of this study is to assess maplirpacept (PF-07901801) administered in combination with PLD in patients with platinum-resistant ovarian cancer and for whom PLD is a reasonable treatment option. The first portion of the study will evaluate the safety of increasing dose levels of maplirpacept (PF-07901801) in combination with PLD at 40 mg/m2 in patients with platinum-resistant EOC (epithelial ovarian cancer). This is a group of cancer, including ovarian, peritoneal, and fallopian tube malignancy. The aim of the first portion of the study is to establish a combination regimen for further assessment in a dose expansion cohort. The study will consist of a 28-day screening period to ensure participants are qualified for the study treatment plan. During the treatment period, patients will receive maplirpacept (PF-07901801) in combination with PLD in 28-day cycles until their disease progresses or unacceptable toxicity develops. There will be a long-term follow-up period in this study to assess overall survival (length of time since start of treatment patients are alive).
Pegylated liposomal doxorubicin (PLD) is a standard treatment option for patients with platinum-resistant ovarian cancer who are not candidates for chemotherapy in combination with bevacizumab. However, despite being consider a standard treatment option, the clinical benefit of chemotherapy for this patient population is small. The goal of this clinical trial is to improve upon the activity of PLD in a safe manner to provide a more effective therapeutic option for this group of patients. C4971002 (TTI-622-02) is a multi-center, open-label study designed to evaluate maplirpacept (PF-07901801) administered in combination with PLD in patients with platinum-resistant ovarian cancer and for whom PLD is a reasonable treatment option. The first portion of the study will evaluate the safety of increasing dose levels of maplirpacept (PF-07901801) in combination with PLD at 40 mg/m2 in patients with platinum-resistant EOC, including ovarian, peritoneal and fallopian tube malignancy, and establish a combination regimen for further evaluation in a dose expansion cohort. The study will consist of a 28-day screening period, a treatment period in which patients will receive maplirpacept (PF-07901801) in combination with PLD in 28-day cycles until documentation of objective disease progression or development of unacceptable toxicity, and a long-term follow-up period to assess overall survival.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
PF-07901801 Escalation (3-dose-level 12, 24, and 48 mg/kg), in combination with Pegylated Liposomal Doxorubicin (40mg/m2) will be administered by intravenous infusion.
RP2D of maplirpacept (PF-07901801) biweekly of maplirpacept (PF-07901801) from Phase 1 escalation in combination with pegylated liposomal doxorubicin 40mg/m2
Sarcoma Oncology Research Center
Santa Monica, California, United States
Baptist Hospital of Miami
Miami, Florida, United States
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, United States
Orlando Health Cancer Institute Gynecologic Cancer Center
Orlando, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Michigan Healthcare Professionals PC
Dearborn, Michigan, United States
Michigan Healthcare Professionals PC
Farmington Hills, Michigan, United States
Michigan Healthcare Professionals PC
Royal Oak, Michigan, United States
Michigan Healthcare Professionals PC
Sterling Heights, Michigan, United States
Cleveland Clinic taussig Cancer Center Investigational Pharmacy
Cleveland, Ohio, United States
...and 8 more locations
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as hematologic and/or non-hematologic treatment-emergent adverse event (TEAE) that occurred during the 28-day Cycle 1 and were judged by the investigator as related to Maplirpacept or the combination of Maplirpacept and PLD. Adverse events (AEs) that were in the opinion of the investigator attributable exclusively to intravenous infusion of PLD or any PLD prophylaxis medication were not considered a DLT.
Time frame: Cycle 1 (28 days)
Phase 1: Number of Participants With TEAEs, Serious TEAEs, >=3 Grade TEAEs, Treatment Related TEAEs, Treatment Related Serious TEAEs and >=3 Grade Treatment Related TEAEs
AE: untoward medical occurrence or the worsening of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to study treatment. TEAEs: event that occurred or worsened on or after start of Maplirpacept up to 30 days (+5) after last dose of study treatment or 1 day before starting day of new anti-cancer drug therapy; includes serious and all non-serious AEs. Serious AE: AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs' severity graded using common terminology criteria for AEs (CTCAE) v 5.0; grade 3= severe; grade 4= life-threatening; grade 5= death. Treatment-related AE: untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by investigator.
Time frame: From start of treatment up to 30 days (+5) after last dose of study treatment or 1 day before starting day of new anti-cancer drug therapy whichever occurred first (up to approximately 33 weeks; maximum exposure of study treatment = 32 weeks)
Phase 1: Change From Baseline in Diastolic and Systolic Blood Pressure (BP) at End of Treatment
BP was measured in millimeter of mercury (mmHg).
Time frame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
Phase 1: Change From Baseline in Respiratory Rate at End of Treatment
Respiratory rate was measured in breaths per minute (breaths/ min).
Time frame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
Phase 1: Change From Baseline in Pulse Rate at End of Treatment
Pulse rate was measured in beats per minute (beats/min).
Time frame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
Phase 1: Change From Baseline in Temperature at End of Treatment
Temperature was measured in degree Celsius (C).
Time frame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
Phase 1: Change From Baseline in Weight at End of Treatment
Weight was measured in kilogram (kg).
Time frame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Standard 12-lead ECGs utilizing limb leads were used to interpret normal and abnormal results, QT interval. ECG was performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG abnormalities were determined by the investigator.
Time frame: During study treatment, (maximum up to 32 weeks)
Phase 1: Phase 1: Number of Participants With Shift to Grade 3/4 in Serum Chemistry Parameters Abnormalities From Baseline to Post-baseline During the Study Treatment
Serum chemistry tests included determination of the following parameters: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, indirect bilirubin, uric acid, calcium, magnesium, and lactate dehydrogenase (LDH). The serum chemistry parameters were graded using CTCAE version 5.0. The intensity was assigned a grade of 1-5 using the following CTCAE guidelines: grade 1= mild; grade 2= moderate; grade 3= severe; grade 4= life-threatening; grade 5= death. In this outcome measure number of participants with at least 1 event of shift to grade 3 or 4 in serum chemistry parameters abnormalities from baseline to post-baseline during study treatment are reported.
Time frame: Baseline to post-baseline during study treatment (maximum up to 32 weeks)
Phase 1: Number of Participants With Shift to Grade 3/4 in Hematology Parameters Abnormalities From Baseline to Post-baseline During the Study Treatment
Hematology tests included determination of the following parameters: hemoglobin, hematocrit, platelets, white blood cells (WBC), neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, red blood cells (RBC), absolute reticulocytes, reticulocytes percentage (%), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte mean corpuscular volume (MCV), and red cell distribution width (RDW). Clinical significance was determined by the investigator. The hematology parameter was graded using CTCAE version 5.0. The intensity was assigned a grade of 1-5 using the following CTCAE guidelines: grade 1= mild; grade 2= moderate; grade 3= severe; grade 4= life-threatening; grade 5= death. In this outcome measure number of participants with at least 1 event of shift to grade 3 or 4 in hematology parameters abnormalities from baseline to post-baseline during study treatment are reported.
Time frame: Baseline to post-baseline during study treatment (maximum up to 32 weeks)
Phase 1: Number of Participants With Dose Delay
Dose delay was the difference between the actual time between two consecutive non-zero doses and the planned time between the same two consecutive non-zero doses. In this outcome measure number of participants with any event of dose delay are reported.
Time frame: During study treatment, (maximum up to 32 weeks)
Phase 1: Number of Participants Who Discontinued Study Treatment Due to TEAE
In this outcome measure number of participants who discontinued study treatment due to TEAE are reported. TEAEs: event that occurred or worsened on or after start of Maplirpacept up to 30 days (+5) after last dose of study treatment or 1 day before starting day of new anti-cancer drug therapy; includes serious and all non-serious AEs.
Time frame: During study treatment, (maximum up to 32 weeks)
Phase 1: Progression Free Survival (PFS), Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1
PFS: time from the first Maplirpacept infusion (Cycle 1 Day 1) to disease progression (PD) or death of any cause, whichever occurred first. Participants who completed or discontinued the study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, were censored at their last adequate response assessment date or last adequate assessment prior to the start date of alternate anti-cancer therapy. If date of progression occurred on the same date as the start of new anticancer therapy, the progression was counted as an event. PD per RECIST v1.1: at least a 20% increase in the sum of longest diameter (LD) 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 increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of 1 or more new lesions. Analysis was performed using Kaplan-Meier method.
Time frame: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
Phase 1: Overall Survival (OS)
OS was defined as the time from the first Maplirpacept infusion (Cycle 1 Day 1) to death of any cause. Participants without death date at the time of analysis were censored at their last known alive date. Analysis was planned to be performed using Kaplan-Meier method. However, the study was terminated prior to achieving meaningful number of events, hence Kaplan-Meier analysis was not conducted. In this outcome measure number of days from first Maplirpacept infusion until death for each participant (who had death as an event) is reported individually.
Time frame: From first Maplirpacept infusion till death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
Phase 1: Phase 1: Disease Control Rate (DCR), Per RECIST v1.1
DCR: percentage of participants who had achieved complete response (CR), partial response (PR), or stable disease (SD) lasting at least 12 weeks. According to RECIST v1.1 criteria: CR = disappearance of all target lesions, any pathological lymph nodes (whether target or on-target) must have reduction in short axis to \<10 mm; PR = at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; PD = at least a 20% increase in the sum of LD 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. The appearance of 1 or more new lesions.
Time frame: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
Phase 1: Duration of Response (DOR)
DOR: for participants who achieved a confirmed CR or PR; defined as time from the date of first documented response (CR or PR) to the date of documented progression or death of any cause after achieving response. Participants who completed or discontinued the study without PD or death, as well as participants who received alternate anti-cancer therapy prior to PD, was censored at their last adequate response assessment date or last adequate assessment prior to start date of alternate anti-cancer therapy. CR=disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 mm; PR=at least 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; PD= at least 20% increase in the sum of LD of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions.
Time frame: From time of first documented CR or PR to progression or death or censoring date, whichever occurred earlier (maximum up to 32 weeks
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