Trial Outcomes & Findings for Study of Maplirpacept (PF-07901801) in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer (NCT NCT05261490)

There were 2 phases of the study: Phase 1 and 2. Due to business decision the study was terminated, and Phase 2 was not conducted. Hence, results in all sections are reported only for Phase 1 of the study and not for Phase 2.

A total of 10 participants were enrolled and treated in the study (Phase 1).

Study of Maplirpacept (PF-07901801) in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer

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.

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.

BP was measured in millimeter of mercury (mmHg).

Respiratory rate was measured in breaths per minute (breaths/ min).

Pulse rate was measured in beats per minute (beats/min).

Temperature was measured in degree Celsius (C).

Weight was measured in kilogram (kg).

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.

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.

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.

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.

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.

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.

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.

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.

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.