2025-523521-18-00招募中3 期
C6461003 - AN INTERVENTIONAL, PHASE 3, DOUBLE-BLIND, RANDOMIZED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-08634404 IN COMBINATION WITH CHEMOTHERAPY VERSUS BEVACIZUMAB IN COMBINATION WITH CHEMOTHERAPY IN TREATMENT-NAÏVE PARTICIPANTS WITH METASTATIC COLORECTAL CANCER
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 220
- 试验地点
- 51
- 主要终点
- PFS by BICR
研究概览
简要总结
To demonstrate that PF-08634404 + mFOLFOX6 (experimental arm) is superior to bevacizumab + mFOLFOX6 (control arm) in prolonging PFS; To demonstrate that PF 08634404 + mFOLFOX6 (experimental arm) is superior to bevacizumab + mFOLFOX6 (control arm) in prolonging OS.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Participants of childbearing potential (Section 10.4.3) must have a negative serum pregnancy test (minimum sensitivity 25 mIU/mL or equivalent quantitative assay) result within 72 hours prior to the first dose of study treatment. Participants with false positive results and documented verification that the participant is not pregnant are eligible for participation.
- •The participant must provide informed consent.
- •Histological or cytological confirmed colorectal adenocarcinoma.
- •Evidence of Stage IV metastatic disease.
- •Known RAS mutation status per local test (CCI). Participants with unknown RAS status despite attempt to test are eligible for participation.
- •No prior systemic therapy for metastatic disease. Note: Participants with early-stage disease who received prior systemic neoadjuvant or adjuvant chemotherapy and present with reoccurrence/metastatic disease within 6 months of stopping treatment will count as having prior therapy in the metastatic setting and are not eligible.
- •ECOG performance status 0-
- •At least one measurable lesion according to RECIST 1.1 per Investigator assessment. Participants with prior definitive radiotherapy must have measurable disease per RECIST 1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions.
- •Have tumor tissue available, either paraffin block or slides from a core, or excisional biopsy (FNA cell blocks, cytology samples and biopsies containing bone are not adequate). a. See Central Laboratory Manual for tissue specifications, handling, and shipping instructions. b. If less than the required amount of slides as outlined in the laboratory manual are available, the sponsor must be contacted to determine if available slides are sufficient. c. If sufficient archival tissue is not available, a new baseline tumor biopsy with adequate tissue is required, unless medically infeasible and with prior agreement with the medical monitor and documentation submitted to the sponsor.
- •Adequate hematologic, hepatic, and renal function by meeting the following criteria a. Participants must meet the hematologic criteria below without the use of transfusions or growth factors (platelet or red blood cell transfusions, TPO, EPO, G-CSF, IL-11, etc.) within 7 days prior to screening laboratory tests.
排除标准
- •Locally confirmed BRAF V600E mutation
- •Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to first dose including but not limited to the following: a. Unstable angina b. Myocardial infarction c. Uncontrolled or significant arrhythmia (including sustained ventricular tachyarrhythmia and ventricular fibrillation), untreated serious conduction system abnormalities (eg, bifascicular block [defined as right bundle branch and left anterior or posterior hemiblock], 3rd degree AV block) d. Coronary/peripheral artery bypass graft e. Transient ischemic attack, cerebrovascular accident, cerebral infarction (excluding lacunar infarction), or cerebral hemorrhage f. Symptomatic congestive heart failure or symptoms consistent with NYHA Functional Class II or higher g. Baseline QTcF interval > 480 msec • If QTcF exceeds 480 msec, the ECG is to be repeated twice and the average of the 3 QTcF values should be used to determine the participant’s eligibility. Computer-interpreted ECGs with abnormal findings should be overread by an investigator physician experienced in reading ECGs before excluding participants. h. Decompensated liver cirrhosis i. Nephrotic syndrome j. Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, or poor compliance with antihypertensive medications) k. Arterial thromboembolic event and venous thromboembolic event Grade ≥3 as specified in CTCAE 5.0 l. Hypertensive crisis m. Hypertensive encephalopathy
- •Participants with active autoimmune diseases requiring systemic treatment within the past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs): a. Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is allowed. b. Participants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per exclusion criterion 11), or resolved childhood asthma/atopy are allowed. c. Participants with Sjögren’s syndrome are allowed.
- •Evidence of non-infectious or drug-induced ILD pneumonitis that: • Was previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks, or; • Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or; • Is currently diagnosed and managed with systemic therapy, or; • Is suspected on radiologic imaging at screening.
- •Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1, or to levels specified in the inclusion/exclusion criteria, with the exception of alopecia. Participants who experience irreversible toxicity that is not expected to worsen with continued administration of the study intervention (eg, hearing loss) may be enrolled in the study after consultation with the medical monitor. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study after consultation with the medical monitor.
- •Grade ≥3 baseline neuropathy, or ongoing residual Grade ≥2 neuropathy from prior oxaliplatin.
- •History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.
- •Participants with any 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. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥ 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Participants with a history of other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after consultation with sponsor or designee.
- •Known or suspected hypersensitivity to any component of study intervention or their excipients at the planned doses.
- •Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.
- •Locally confirmed MSI-high or dMMR colorectal cancer
- •Participants with known active symptomatic CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression Note: Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be enrolled if all of the following are met: a. CNS metastases have been clinically stable with no evidence of clinical or radiographic disease progression for ≥14 days after completion of definitive radiotherapy and/or surgery and prior to study intervention. b. The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention.
- •Known DPD deficiency (refer to the local 5-FU label or local clinical guidance for DPD status recommendation prior to starting treatment).
- •Clinically significant risk of hemorrhage or fistula including but not limited to the following: a. Significant tumor necrosis or cavitation b. The investigator deems that participation in the study poses a risk of hemorrhage; c. Tumor invasion or compression of surrounding critical organs (such as aorta, heart and pericardium, superior vena cava, trachea, and esophagus) or a risk of developing tracheoesophageal or pleuroesophageal fistula d. Mediastinal lymph node metastasis with invasion of the trachea or main bronchi. If centrally located mediastinal masses (<30 mm from the carina) identified by CT scan or chest x-ray, CT scan with intravenous contrast or MRI within 21 days prior to randomization must exclude major airway or blood vessel invasion by tumor.
- •Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study; minor local surgery (excluding peripherally inserted central catheter placement and implantable central venous port placement) within 3 days prior to the first dose. Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting study intervention.
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •Any Grade ≥3 bleeding/hemorrhage events within 28 days of Cycle 1 Day 1, or prior history of clinically significant bleeding events, including unhealed wounds following surgical procedure.
- •Participants with acute, chronic or symptomatic infections including: a. Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted. b. Known seropositivity of HIV, except for participants with controlled HIV infection on a stable regimen of ART (CD4+ count >200/mm3 and viral load of <400 copies/mL). The investigator will ensure the ART does not result in substantial interactions with study or concomitant medications. c. Known active HBV infection by positive HBV surface antigen. d. Active HCV infection (positive HCV viral load by PCR). Participants who have been treated for HCV infection are eligible if they have documented sustained virologic response 12 weeks after completion of antiviral therapy. Note: Testing for HIV, HBV, or HCV is not required unless mandated by local health authorities. e. Participants with known active TB infection • Participants suspected to have active TB are required to undergo clinical evaluation to rule out the condition.
研究组 & 干预措施
PF-08634404
Test
干预措施: PF-08634404 (Drug)
FLUOROURACIL
Test
干预措施: FLUOROURACIL (Drug)
BEVACIZUMAB
Comparator
干预措施: BEVACIZUMAB (Drug)
OXALIPLATIN
Test
干预措施: OXALIPLATIN (Drug)
CALCIUM FOLINATE
Test
干预措施: CALCIUM FOLINATE (Drug)
结局指标
主要结局
PFS by BICR
PFS by BICR
OS
OS
次要结局
- • PFS by investigator • ORR by BICR and by investigator • DOR by BICR and by investigator • PFS2 (PFS after next-line therapy) by investigator
- • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study intervention. • Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing.
- • Predose and postdose concentrations of PF-08634404
- • Incidence of ADA against PF-08634404
- • Mean score change from baseline in participant reported GHS/QoL, function, and symptoms per EORTC QLQ-C30 • Mean score change from baseline in participant reported function and symptoms scales per EORTC QLQ-CR29
- • Time to definitive deterioration in participant reported GHS/QoL, function and symptoms per EORTC QLQ-C30 • Time to definitive deterioration in participant reported function and symptoms per EORTC QLQ-CR29
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (51)
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