2025-524717-86-00招募中3 期
C6461016 - A PHASE 2/3 INTERVENTIONAL STUDY OF PF-08634404 IN COMBINATION WITH CHEMOTHERAPY IN TREATMENT-NAÏVE PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC GASTRIC, GASTROESOPHAGEAL JUNCTION, OR ESOPHAGEAL ADENOCARCINOMA
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 91
- 试验地点
- 6
- 主要终点
- Phase 3; PFS using RECIST 1.1 as assessed by BICR
研究概览
简要总结
Phase 2
- To evaluate antitumor activity of PF-08634404 in combination with chemotherapy.
- To evaluate safety and tolerability of PF-08634404 in combination with chemotherapy. Phase 3
- To demonstrate that PF-08634404 in combination with chemotherapy (experimental arm) is superior to nivolumab in combination with chemotherapy (control arm) in prolonging PFS by Blinded Independent Central Review (BICR).
- To demonstrate that PF-08634404 in combination with chemotherapy (experimental arm) is superior to nivolumab in combination with chemotherapy (control arm) in prolonging OS.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ 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.
- •Histologically or cytologically confirmed diagnosis of gastric, gastroesophageal junction, or esophageal adenocarcinoma, with evidence of locally advanced unresectable or metastatic disease.
- •For Phase 2: 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. For Phase 3: At least one evaluable lesion according to RECIST 1.1 per investigator.
- •No prior systemic therapy for advanced or metastatic disease.
- •ECOG PS score of 0 or
- •Sufficient tumor tissue available to submit for correlative studies, either as an FFPE tumor tissue block, or slides containing unstained FFPE tumor tissue sections, from a core or excisional biopsy (cytology samples, including cell blocks generated from FNA biopsies, and biopsies containing bone are not adequate).
- •Participants whose tumors express PD-L1 (TAP ≥1% or CPS ≥1) based on local testing results.
- •HER2-negative status based on local testing results.
- •Adequate hematologic, hepatic, and renal function.
排除标准
- •Participants have squamous cell or undifferentiated gastroesophageal cancer.
- •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.
- •Unresolved toxicities from prior antitumor therapy that did not recover to NCI CTCAE version 5.0 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 >1 baseline peripheral neuropathy.
- •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.
- •Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
- •Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to the first dose.
- •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.
- •Participants with active autoimmune diseases requiring systemic treatment within the past 2 years prior to the first dose of study intervention (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). a) Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is permitted. b)Participants with vitiligo, psoriasis, type 1 diabetes mellitus or resolved childhood asthma/atopy are allowed. c) Participants with Sjögren’s syndrome are allowed.
- •Participants with known active CNS metastases, including leptomeningeal, brainstem, meningeal or spinal cord metastases or compression are excluded.
- •Known DPD deficiency (refer to the local 5-FU and capecitabine label or local clinical guidance for DPD status recommendation prior to starting treatment).
- •Clinically significant risk of hemorrhage or fistula.
- •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.
研究组 & 干预措施
OXALIPLATIN
Test
干预措施: OXALIPLATIN (Drug)
FLUOROURACIL
Test
干预措施: FLUOROURACIL (Drug)
PF-08634404
Test
干预措施: PF-08634404 (Drug)
CALCIUM FOLINATE
Test
干预措施: CALCIUM FOLINATE (Drug)
CAPECITABINE, CAPECITABINE
Test
干预措施: CAPECITABINE (Drug)
SODIUM CHLORIDE
Placebo
干预措施: SODIUM CHLORIDE (Drug)
NIVOLUMAB
Comparator
干预措施: NIVOLUMAB (Drug)
结局指标
主要结局
Phase 3; PFS using RECIST 1.1 as assessed by BICR
Phase 3; PFS using RECIST 1.1 as assessed by BICR
Phase 3; OS
Phase 3; OS
Phase 2; Confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by investigator
Phase 2; Confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by investigator
Phase 2; Adverse events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0), timing, seriousness, and relationship to study intervention
Phase 2; Adverse events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0), timing, seriousness, and relationship to study intervention
次要结局
- Phase 2; - Duration of response (DOR) using RECIST 1.1 as assessed by investigator - Progression-free survival (PFS) using RECIST 1.1 as assessed by investigator - Overall survival (OS)
- Phase 2; Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
- Phase 2; Predose and postdose concentrations of PF-08634404
- Phase 2; Incidence of anti-drug antibodies (ADA) against PF-08634404
- Phase 3; - ORR using RECIST 1.1 as assessed by BICR and by investigator - PFS using RECIST 1.1 as assessed by investigator - DOR using RECIST 1.1 as assessed by BICR and by investigator - PFS2 (PFS after
- Phase 3; - AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s) - Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing
- Phase 3; Predose and postdose concentrations of PF-08634404
- Phase 3; Incidence of ADA against PF- 08634404
- Phase 3; - Change from baseline in Functional Assessment of Cancer Therapy – Gastric (FACT-Ga) Total score and Gastric Cancer Subscale (GaCS) score - Time to definitive deterioration in FACT-Ga total score - Time to definitive deterioration in Gastric
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (6)
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