A Phase Ⅰ/Ⅱ Study of TTI-622 in Combination With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 10
- 试验地点
- 15
- 主要终点
- Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase 1: Dose Escalation
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.
干预措施: maplirpacept (PF-07901801) (Drug)
Phase 1: Dose Escalation
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.
干预措施: Pegylated Liposomal Doxorubicin (PLD) (Drug)
Phase 2: Dose Expansion
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.
干预措施: maplirpacept (PF-07901801) (Drug)
Phase 2: Dose Expansion
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.
干预措施: Pegylated Liposomal Doxorubicin (PLD) (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (28 days)
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.
次要结局
- 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))
- Phase 1: Change From Baseline in Weight 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))
- Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities(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(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(Baseline to post-baseline during study treatment (maximum up to 32 weeks))
- Phase 1: Number of Participants With Dose Delay(During study treatment, (maximum up to 32 weeks))
- Phase 1: Number of Participants Who Discontinued Study Treatment Due to TEAE(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(From first Maplirpacept infusion till PD or death or censoring date, whichever occurred earlier (maximum up to 32 weeks))
- Phase 1: Overall Survival (OS)(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(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)(From time of first documented CR or PR to progression or death or censoring date, whichever occurred earlier (maximum up to 32 weeks)