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Ovarian CancerPhase 1/2NCT05261490

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

A Phase 1/2 study testing maplirpacept (PF-07901801) and Pegylated Liposomal Doxorubicin (PLD) in people with Ovarian Cancer and Ovarian Neoplasms, run by Pfizer at 18 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
maplirpacept (PF-07901801) and Pegylated Liposomal Doxorubicin (PLD)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
18 sitesUnited States
Study dates
1 Aug 2022to 15 Feb 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Histologically-confirmed epithelial ovarian cancer (EOC), fallopian tube carcinoma (FTC) or primary peritoneal carcinomas (PPC).
  • Platinum-resistant recurrent (disease progression ≤6 months after the most recent platinum-based treatment regimen (date calculated from the last administered dose of platinum) or the participant is no longer able to receive.
  • or declined treatment with platinum-based chemotherapy.
  • Progression with standard of care therapies, including platinum-based therapies, poly ADP ribose polymerase (PARP) inhibitors or bevacizumab in the platinum-sensitive setting or intolerability to such therapies or patient refusal
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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  • Adequate organ and hematologic function
  • No more than four prior treatment regimens for platinum-resistant disease
  • All adverse events from prior treatment must be the Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.

Who cannot join

  • Platinum-refractory disease (defined as progression on or within 3 months of completing primary first-line platinum-based treatment)
  • Non-epithelial histology, including malignant mixed Mullerian tumors
  • Ovarian tumors with low malignant potential (i.e., borderline tumors), low grade serous ovarian cancer or carcinosarcoma
  • History of acute coronary syndromes.
  • History of or current Class II, III, or IV heart failure.
  • History or evidence of known central nervous system (CNS) metastases or carcinomatous meningitis.
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  • Significant bleeding disorders, vasculitis or a significant bleeding episode from the Gastrointestinal (GI) tract.
  • History of severe hypersensitivity reactions to antibodies.
  • Systemic steroid therapy.
  • History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
  • Prior organ transplantation including allogenic or autologous stem cell transplantation
  • Prior treatment with anti-cluster of differentiation 47 (CD47) or anti-SIRPα therapy.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites
  • Cleveland Clinic taussig Cancer Center Investigational Pharmacy

    Cleveland, Ohio, 44106

  • Cleveland Clinic Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Michigan Healthcare Professionals PC

    Dearborn, Michigan, 48126

  • Michigan Healthcare Professionals PC

    Farmington Hills, Michigan, 48334

  • oncology Consultants, P.A.

    Houston, Texas, 77024

  • Cleveland Clinic Hillcrest Hospital

    Mayfield Heights, Ohio, 44124

  • Baptist Hospital of Miami

    Miami, Florida, 33176

  • Miami Cancer Institute at Baptist Health, Inc.

    Miami, Florida, 33176

  • Orlando Health Cancer Institute Gynecologic Cancer Center

    Orlando, Florida, 32806

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Magee-Womens Hospital of UPMC

    Pittsburgh, Pennsylvania, 15213

  • UPMC Hillman Cancer Center-Investigational Drug Services

    Pittsburgh, Pennsylvania, 15232

  • Michigan Healthcare Professionals PC

    Royal Oak, Michigan, 48073

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Michigan Healthcare Professionals PC

    Sterling Heights, Michigan, 48314

  • Oklahoma Cancer Specialist and Research Institute. LLC

    Tulsa, Oklahoma, 74146

Other trials in United States

About this study

Official title: A Phase Ⅰ/Ⅱ Study of TTI-622 in Combination With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

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).

Read the detailed description

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.

Being tested
maplirpacept (PF-07901801), Pegylated Liposomal Doxorubicin (PLD)
Keywords
Epithelial Ovarian Cancer (EOC), Ovarian Cancer, Platinum-Resistant Ovarian Cancer, Cluster of Differentiation 47 (CD47), maplirpacept (PF-07901801), TTI-622, Doxorubicin, Immune-oncology, chemotherapy, anti-SIRPα therapy
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • maplirpacept (PF-07901801)Drug

    Also called TTI-622

    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.

  • Pegylated Liposomal Doxorubicin (PLD)Drug

    Also called PLD

    RP2D of maplirpacept (PF-07901801) biweekly of maplirpacept (PF-07901801) from Phase 1 escalation in combination with pegylated liposomal doxorubicin 40mg/m2

Study groups in NCT05261490
Study groupRoleWhat they receive
Phase 1: Dose EscalationExperimentalIn the Phase 1 (dose escalation): Cycle 1 for dose levels 1 and 2, maplirpacept (PF-07901801) will be administered on Day 1, Day 8, Day 15 and Day 22 in combination with PLD on Day 1 of 28-day cycle. Beginning with Cycle 2 at dose levels 1 and 2, maplirpacept (PF-07901801) will be administered on Day 1 and Day 15 in combination with PLD on Day 1 of 28-day cycles. For Phase 1, dose level 3, maplirpacept (PF-07901801) will be administered on Day 1 and Day 15 in combination with PLD on Day 1 of 28-day cycles. Dose level 3 will be biweekly regimen from the start.
Receives: Drug: maplirpacept (PF-07901801); Drug: Pegylated Liposomal Doxorubicin (PLD)
Phase 2: Dose ExpansionExperimentalIn the Phase 2 (dose expansion): maplirpacept (PF-07901801) will be administered with selected dose from the escalation phase by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles in combination with Pegylated Liposomal Doxorubicin 40 mg/m2 by intravenous infusion on Day 1 of each 28-day cycle.
Receives: Drug: maplirpacept (PF-07901801); Drug: Pegylated Liposomal Doxorubicin (PLD)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (28 days)

Secondary outcomes (15)
  1. 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.

    Measured: 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)

  2. Phase 1: Change From Baseline in Diastolic and Systolic Blood Pressure (BP) at End of Treatment

    BP was measured in millimeter of mercury (mmHg).

    Measured: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)

  3. Phase 1: Change From Baseline in Respiratory Rate at End of Treatment

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

    Measured: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)

  4. Phase 1: Change From Baseline in Pulse Rate at End of Treatment

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

    Measured: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)

  5. Phase 1: Change From Baseline in Temperature at End of Treatment

    Temperature was measured in degree Celsius (C).

    Measured: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)

  6. Phase 1: Change From Baseline in Weight at End of Treatment

    Weight was measured in kilogram (kg).

    Measured: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)

  7. 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.

    Measured: During study treatment, (maximum up to 32 weeks)

  8. 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.

    Measured: Baseline to post-baseline during study treatment (maximum up to 32 weeks)

  9. 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.

    Measured: Baseline to post-baseline during study treatment (maximum up to 32 weeks)

  10. 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.

    Measured: During study treatment, (maximum up to 32 weeks)

  11. 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.

    Measured: During study treatment, (maximum up to 32 weeks)

  12. 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.

    Measured: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)

  13. 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.

    Measured: From first Maplirpacept infusion till death or censoring date, whichever occurred earlier (maximum up to 32 weeks)

  14. 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.

    Measured: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)

  15. 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.

    Measured: From time of first documented CR or PR to progression or death or censoring date, whichever occurred earlier (maximum up to 32 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2022
  2. Study start1 Aug 2022
  3. Primary completion11 Oct 2023
  4. Study completion15 Feb 2024

Why it stopped: A business decision was made by Pfizer to terminate and remove the Phase 2 expansion of this study for administrative reasons. The reason for study termination is not due to any safety concerns or requests from regulatory authorities.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase 1/2 (dose escalation and dose expansion)
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05261490
Sponsor's protocol ID
TTI-622-02
Other IDs
C4971002
Status last verified
Oct 2024
First submitted
22 Nov 2021
Last updated
19 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing maplirpacept (PF-07901801) and Pegylated Liposomal Doxorubicin (PLD) in people with Ovarian Cancer and Ovarian Neoplasms, run by Pfizer at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.

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