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

NCT05261490 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: TTI-622-02C4971002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 18

Brief 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. 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).

Conditions

Ovarian Cancer; Ovarian Neoplasms; Ovarian Carcinoma; Fallopian Tube Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma

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

Outcome Measures

Primary Outcomes (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.

  Cycle 1 (28 days)

Secondary Outcomes (15)

• 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

  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

  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

  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

  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

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

Study Arms (2)

Phase 1: Dose Escalation

EXPERIMENTAL

In 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.

Drug: maplirpacept (PF-07901801); Drug: Pegylated Liposomal Doxorubicin (PLD)

Phase 2: Dose Expansion

EXPERIMENTAL

In 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.

Drug: maplirpacept (PF-07901801); Drug: Pegylated Liposomal Doxorubicin (PLD)

Interventions

maplirpacept (PF-07901801) DRUG

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.

Also known as: TTI-622

Phase 1: Dose Escalation; Phase 2: Dose Expansion

Pegylated Liposomal Doxorubicin (PLD) DRUG

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

Also known as: PLD

Phase 1: Dose Escalation; Phase 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (18)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Orlando Health Cancer Institute Gynecologic Cancer Center

Orlando, Florida, 32806, United States

Location

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

Michigan Healthcare Professionals PC

Dearborn, Michigan, 48126, United States

Location

Michigan Healthcare Professionals PC

Farmington Hills, Michigan, 48334, United States

Location

Michigan Healthcare Professionals PC

Royal Oak, Michigan, 48073, United States

Location

Michigan Healthcare Professionals PC

Sterling Heights, Michigan, 48314, United States

Location

Cleveland Clinic taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Cleveland Clinic Hillcrest Hospital

Mayfield Heights, Ohio, 44124, United States

Location

Oklahoma Cancer Specialist and Research Institute. LLC

Tulsa, Oklahoma, 74146, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Hillman Cancer Center-Investigational Drug Services

Pittsburgh, Pennsylvania, 15232, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

oncology Consultants, P.A.

Houston, Texas, 77024, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

liposomal doxorubicin; 1-dodecylpyridoxal

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

Due to business decision the study was terminated, and Phase 2 of the study was not conducted. Hence, none of the section reports results for Phase 2 of the study. Data reported is only for Phase 1 of the study.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1/2 (dose escalation and dose expansion)

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: March 2, 2022
• Study Start: August 1, 2022
• Primary Completion: October 11, 2023
• Study Completion: February 15, 2024
• Last Updated: November 19, 2024
• Results First Posted: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (18)