An Open-label Phase 1 Study to Investigate PF-08046050 (SGN-CEACAM5C) in Adults With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- 5-Fluorouracil (5-FU)
- 疾病 / 适应症
- Colorectal Neoplasms
- 发起方
- Seagen, a wholly owned subsidiary of Pfizer
- 入组人数
- 914
- 试验地点
- 65
- 主要终点
- Number of participants with adverse events (AEs)
- 状态
- 招募中
- 最后更新
- 12天前
概览
简要总结
This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat.
Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs.
This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells.
This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body.
This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.
研究者
入排标准
入选标准
- •Tumor type:
- •Participants in Part A (dose escalation) and Part B (dose optimization) must have histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancy. Must have relapsed, refractory, or progressive disease, and should have no appropriate standard therapy available.
- •Participants in Part A must have one of the following tumor types: colorectal cancer (CRC); gastric carcinoma (GC) or gastroesophageal junction adenocarcinoma (GEJ); non-small cell lung cancer (NSCLC); or pancreatic ductal adenocarcinoma (PDAC).
- •The tumor types to be enrolled in Part B will be identified by the sponsor from among those specified in Part A.
- •Participants in Part C (dose expansion) must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor malignancies.
- •CRC (adenocarcinoma of the colon or rectum) and must have received no more than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and evidence of either progressive disease or intolerance to their last regimen.
- •PDAC with one or more metastatic lesions measurable by computed tomography/magnetic resonance imaging according to RECIST v1.1 criteria; and must have received no more than 1 prior chemotherapy regimen for the treatment of advanced PDAC and evidence of either progressive disease or intolerance to that regimen.
- •GC or GEJ and must have received prior platinum and fluoropyrimidine-based chemotherapy.
- •NSCLC and must have received platinum-based therapy. If eligible and consistent with local standard of care must have received a PD-1/PD-L1 inhibitor. In addition, participants with tumor genomic mutations/alterations for which approved targeted therapies are available per local standard of care, must have received such therapies.
- •Small cell lung cancer (SCLC) and must have received platinum-based therapy for extensive-stage disease and no more than 3 prior lines of therapy. If eligible and consistent with local standard of care must have received a PD 1/PD-L1 inhibitor.
排除标准
- •Previous exposure to CEACAM5-targeted therapy.
- •Prior treatment with a TOPO1-targeting ADC (CPT payload), such as Enhertu (trastuzumab deruxtecan) or Trodelvy (sacituzumab govitecan).
- •History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
- •Active cerebral/meningeal disease related to the underlying malignancy. Participants with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior central nervous system disease has been treated and the participant is clinically stable (defined as not having received steroid treatment for symptoms related to cerebral/meningeal disease for at least 2 weeks prior to enrollment and with no ongoing related AEs).
- •\> Criteria related to bevacizumab administration (participants in Parts D and E)
- •History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
- •History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
- •Serious non-healing wound, non-healing ulcer, or non-healing bone fracture.
- •Deep venous thromboembolic event within 4 weeks prior to enrollment
- •Known coagulopathy that increases risk of bleeding, bleeding diatheses.
研究组 & 干预措施
PF-08046050 + bevacizumab + 5FU/LV
PF-08046050 combination with bevacizumab + 5FU/LV
干预措施: 5-Fluorouracil (5-FU)
PF-08046050 + bevacizumab + 5FU/LV
PF-08046050 combination with bevacizumab + 5FU/LV
干预措施: Leucovorin (LV)
PF-08046050 + 5FU/LV + oxaliplatin
PF-08046050 combination with 5FU/LV + oxaliplatin
干预措施: Leucovorin (LV)
PF-08046050 + 5FU/LV
PF-08046050 combination with 5FU/LV
干预措施: 5-Fluorouracil (5-FU)
PF-08046050 + 5FU/LV
PF-08046050 combination with 5FU/LV
干预措施: Leucovorin (LV)
PF-08046050 +bevacizumab
PF-08046050 combination with bevacizumab
干预措施: PF-08046050
PF-08046050
PF-08046050 monotherapy
干预措施: PF-08046050
PF-08046050 +bevacizumab
PF-08046050 combination with bevacizumab
干预措施: bevacizumab
PF-08046050 + bevacizumab + 5FU/LV
PF-08046050 combination with bevacizumab + 5FU/LV
干预措施: PF-08046050
PF-08046050 + bevacizumab + 5FU/LV
PF-08046050 combination with bevacizumab + 5FU/LV
干预措施: bevacizumab
PF-08046050 + 5FU/LV + oxaliplatin
PF-08046050 combination with 5FU/LV + oxaliplatin
干预措施: PF-08046050
PF-08046050 + 5FU/LV + oxaliplatin
PF-08046050 combination with 5FU/LV + oxaliplatin
干预措施: Oxaliplatin
PF-08046050 + 5FU/LV + oxaliplatin
PF-08046050 combination with 5FU/LV + oxaliplatin
干预措施: 5-Fluorouracil (5-FU)
PF-08046050 + 5FU/LV + oxaliplatin + bevacizumab
PF-08046050 combination with 5FU/LV + oxaliplatin + bevacizumab
干预措施: Leucovorin (LV)
PF-08046050 + 5FU/LV + oxaliplatin + bevacizumab
PF-08046050 combination with 5FU/LV + oxaliplatin + bevacizumab
干预措施: Oxaliplatin
PF-08046050 + 5FU/LV + oxaliplatin + bevacizumab
PF-08046050 combination with 5FU/LV + oxaliplatin + bevacizumab
干预措施: 5-Fluorouracil (5-FU)
PF-08046050 + 5FU/LV + oxaliplatin + bevacizumab
PF-08046050 combination with 5FU/LV + oxaliplatin + bevacizumab
干预措施: PF-08046050
PF-08046050 + 5FU/LV + oxaliplatin + bevacizumab
PF-08046050 combination with 5FU/LV + oxaliplatin + bevacizumab
干预措施: bevacizumab
PF-08046050 + 5FU/LV
PF-08046050 combination with 5FU/LV
干预措施: PF-08046050
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: Through 30-37 days after the last study treatment, up to approximately 2 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention
Number of dose modifications due to AEs
时间窗: Through end of treatment up to approximately 2 years
Number of participants with laboratory abnormalities
时间窗: Through 30-37 days after the last study treatment, up to approximately 2 years
Number of participants with dose-limiting toxicities (DLTs)
时间窗: Up to 28 days
Number of participants with DLTs by dose level
时间窗: Up to 28 days
次要结局
- Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)(Through 30-37 days after the last study treatment, up to approximately 2 years)
- Best overall response(Through end of study and up to approximately 2 years)
- Overall survival (OS)(Through end of study and up to approximately 2 years)
- PK parameter - Maximum concentration (Cmax)(Through 30-37 days after the last study treatment, up to approximately 2 years)
- Duration of response (DOR)(Through end of study and up to approximately 2 years)
- PK parameter - Time to maximum concentration (Tmax)(Through 30-37 days after the last study treatment, up to approximately 2 years)
- Number of participants with antidrug antibodies (ADAs)(Through 30-37 days after the last study treatment, up to approximately 2 years)
- Objective response rate (ORR)(Through end of study and up to approximately 2 years)
- Progression-free survival (PFS)(Through end of study and up to approximately 2 years)
- PK parameter - Trough concentration (Ctrough)(Through 30-37 days after the last study treatment, up to approximately 2 years)