Clinical trial NCT05261490: Study of Maplirpacept (PF-07901801) in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer
Official title: A Phase Ⅰ/Ⅱ Study of TTI-622 in Combination With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1/2 (dose escalation and dose expansion)
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (28 days)
Secondary outcomes:
measure: 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
timeFrame: 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)
measure: Phase 1: Change From Baseline in Diastolic and Systolic Blood Pressure (BP) at End of Treatment
timeFrame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
measure: Phase 1: Change From Baseline in Respiratory Rate at End of Treatment
timeFrame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
measure: Phase 1: Change From Baseline in Pulse Rate at End of Treatment
timeFrame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
measure: Phase 1: Change From Baseline in Temperature at End of Treatment
timeFrame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
measure: Phase 1: Change From Baseline in Weight at End of Treatment
timeFrame: Baseline (prior to the start of study treatment on Day 1 Cycle 1), End of treatment (maximum up to 32 weeks)
measure: Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: During study treatment, (maximum up to 32 weeks)
measure: 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
timeFrame: Baseline to post-baseline during study treatment (maximum up to 32 weeks)
measure: Phase 1: Number of Participants With Shift to Grade 3/4 in Hematology Parameters Abnormalities From Baseline to Post-baseline During the Study Treatment
timeFrame: Baseline to post-baseline during study treatment (maximum up to 32 weeks)
measure: Phase 1: Number of Participants With Dose Delay
timeFrame: During study treatment, (maximum up to 32 weeks)
measure: Phase 1: Number of Participants Who Discontinued Study Treatment Due to TEAE
timeFrame: During study treatment, (maximum up to 32 weeks)
measure: Phase 1: Progression Free Survival (PFS), Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1
timeFrame: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
measure: Phase 1: Overall Survival (OS)
timeFrame: From first Maplirpacept infusion till death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
measure: Phase 1: Phase 1: Disease Control Rate (DCR), Per RECIST v1.1
timeFrame: From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)
measure: Phase 1: Duration of Response (DOR)
timeFrame: From time of first documented CR or PR to progression or death or censoring date, whichever occurred earlier (maximum up to 32 weeks
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute Gynecologic Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Dearborn
country: United States
facility: Michigan Healthcare Professionals PC
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Healthcare Professionals PC
state: Michigan
city: Royal Oak
country: United States
facility: Michigan Healthcare Professionals PC
state: Michigan
city: Sterling Heights
country: United States
facility: Michigan Healthcare Professionals PC
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic taussig Cancer Center Investigational Pharmacy
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clinic Hillcrest Hospital
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialist and Research Institute. LLC
state: Oklahoma
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center-Investigational Drug Services
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Houston
country: United States
facility: oncology Consultants, P.A.
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: