A PHASE 1A/B OPEN-LABEL MASTER STUDY OF PF-07799544 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER TARGETED AGENTS IN PARTICIPANTS WITH BRAF-MUTANT MELANOMA AND OTHER SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 148
- 试验地点
- 172
- 主要终点
- Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with treatment-emergent adverse events (AEs)
研究概览
简要总结
The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b).
Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have:
- a solid tumor which is metastatic or recurrent (excluding colorectal cancer)
- tumor with the mutation (abnormal gene) called "BRAF V600"
- received required prior treatment for cancer per cohort assigned.
All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day.
Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 1b Inclusion Criteria:
- •Diagnosis of advanced/metastatic solid tumor (excluding colorectal cancer)
- •Measurable disease by RECIST version 1.1
- •Evidence of a BRAF V600 mutation
- •Prior therapy per tumor cohort
- •Adequate organ function per protocol
排除标准
- •Other active malignancy within 3 years
- •Presence of leptomeningeal disease
- •History or current evidence of retinal vein occlusion (RVO) or history of retinal degenerative disease
- •Concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
- •Active gastrointestinal disease as defined per protocol
- •History of interstitial lung disease as defined per protocol
研究组 & 干预措施
Phase 1b Combination Dose Escalation
Participants will receive PF-07799544 and PF-07799933
干预措施: PF-07799544 (Drug)
Phase 1a Monotherapy Dose Escalation
Participants will receive PF-07799544
干预措施: PF-07799544 (Drug)
Phase 1b Combination Dose Escalation
Participants will receive PF-07799544 and PF-07799933
干预措施: PF-07799933 (Drug)
Phase 1b Combination Dose Expansion
Participants will receive PF-07799544 and PF-07799933
干预措施: PF-07799544 (Drug)
Phase 1b Combination Dose Expansion
Participants will receive PF-07799544 and PF-07799933
干预措施: PF-07799933 (Drug)
结局指标
主要结局
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with treatment-emergent adverse events (AEs)
时间窗: Baseline to 28 days after last dose of study medication
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in laboratory abnormalities
时间窗: Baseline to 28 days after last dose of study treatment
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in vital sign abnormalities
时间窗: Baseline to 28 days after last dose of study treatment
Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Phase 1b Dose Expansion: Overall response rate (ORR)
时间窗: Baseline to 2 years
Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with dose limiting toxicities (DLTs)
时间窗: Cycle 1 (21 days)
DLTs will be evaluated during the first cycle (21 days) as a single agent (phase 1a monotherapy) or in combination with other agents (phase 1b dose escalation)
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with treatment-emergent adverse events (AEs)
时间窗: Baseline to 28 days after last dose of study medication
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in laboratory abnormalities
时间窗: Baseline to 28 days after last dose of study treatment
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in vital sign abnormalities
时间窗: Baseline to 28 days after last dose of study treatment
Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in physical exam abnormalities
时间窗: Baseline to 28 days after last dose of study treatment
Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Phase 1b Dose Expansion: Overall response rate (ORR)
时间窗: Baseline to 2 years
Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors
次要结局
- PK Parameters: terminal elimination half-life (t½)(Baseline to 2 years)
- PK Parameters: Apparent Oral Clearance (CL/F)(Baseline to 2 years)
- Phase 1a monotherapy and Phase 1b combination dose escalation: ORR(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs)(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in vital sign abnormalities(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in laboratory abnormalities(Baseline to 2 years)
- Phase 1b Dose Expansion: Duration of Response (Overall and in CNS)(Baseline to 2 years)
- Phase 1b Dose Expansion: Intracranial response(Baseline to 2 years)
- Phase 1b Dose Expansion: Progression Free Survival (PFS)(Baseline to 2 years)
- PK Parameters: Maximum Plasma Concentration (Tmax)(Baseline to 2 years)
- PK Parameters: Area Under Curve (AUC)(Baseline to 2 years)
- Phase 1a monotherapy and Phase 1b combination dose escalation: ORR(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs)(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in vital sign abnormalities(Baseline to 2 years)
- Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in laboratory abnormalities(Baseline to 2 years)
- Phase 1b Dose Expansion: Duration of Response (Overall and in CNS)(Baseline to 2 years)
- Phase 1b Dose Expansion: Intracranial response(Baseline to 2 years)
- Phase 1b Dose Expansion: Progression Free Survival (PFS)(Baseline to 2 years)
- PK Parameters: Maximum Observed Concentration (Cmax)(Baseline to 2 years)
- PK Parameters: Maximum Plasma Concentration (Tmax)(Baseline to 2 years)
- PK Parameters: Area Under Curve (AUC)(Baseline to 2 years)
- PK Parameters: terminal elimination half-life (t½)(Baseline to 2 years)
- PK Parameters: Apparent Oral Clearance (CL/F)(Baseline to 2 years)
- PK Parameters: Apparent Volume of Distribution (Vz/F)(Baseline to 2 years)