A Phase 1 Study of PF-08046054/SGN-PDL1V in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 714
- 试验地点
- 117
- 主要终点
- Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
This study will test the safety of a drug called PF-08046054/SGN-PDL1V alone and with pembrolizumab in participants with solid tumors. It will also study the side effects of this drug. A side effect is anything a drug does to your body besides treating your disease.
Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).
This study will have five parts. Parts A and B of the study will find out how much PF-08046054/SGN- PDL1V should be given to participants. Part C will use the dose found in Parts A and B to find out how safe PF-08046054/SGN-PDL1V is and if it works to treat solid tumor cancers. In Part D and E, participants will be given PF-08046054/SGN-PDL1V with pembrolizumab to find out how safe this combination is and if it works to treat solid tumor cancers.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Parts A and B:
- •Participants must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor types
- •Non-small cell lung cancer (NSCLC)
- •Head and neck squamous cell carcinoma (HNSCC) (except nasopharyngeal cancer)
- •Esophageal squamous cell carcinoma (SCC)
- •Triple negative breast cancer (TNBC)
- •Participants must have disease that is relapsed or refractory, that has progressed on approved therapies, be intolerant to or refused such therapies, or such and therapies are contraindicated and in the judgement of the investigator, should have no appropriate SoC therapeutic option
- •Participants must have PD-L1 expression based on historical testing
- •Participants must have disease that is relapsed or refractory or be intolerant to SoC therapies and must have one of the following tumor types
- •Participants with HNSCC must have histologically or cytologically-confirmed HNSCC
- •Participants must have histologically or cytologically-confirmed NSCLC. Participants with SCC and non--SCC histology are eligible. Note: Participants with a neuroendocrine component or histology are not eligible.
- •Esophageal SCC
- •Pancreatic cancer
- •Hepatocellular carcinoma
- •Gastric cancer
- •Endometrial cancer
- •Participants must have been previously tested for PD-L1 expression and should have PD-L1 expression ≥1 or <1 by CPS or TPS based on historical testing
- •Part D and Part E:
- •Participants must have histologically or cytologically-confirmed disease of the HNSCC or NSCLC
- •Participants must have PD-L1 expression based on historical testing
- •Participants with NSCLC; PD-L1 expression ≥ 1% by TPS
- •Participants with HNSCC; PD--L1 expression ≥1 by CPS
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Measurable disease per RECIST v1.1 at baseline
排除标准
- •History of another malignancy within 3 years of first dose of study treatment or any evidence of residual disease from a previously diagnosed malignancy.
- •Known active central nervous system metastases. Participants with previously-treated brain metastases may participate provided they:
- •Are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment
- •Have no new or enlarging brain metastases
- •And are off of corticosteroids prescribed for symptoms associate with brain metastases for at least 7 days prior to first dose of study treatment
- •Lepto-meningeal disease
- •Prior treatment with an anti-PD-L1 agent within less than 5 half-lives. This duration of time will vary according to the half-life of the specific agent.
- •Previous receipt of an monomethylauristatin E (MMAE)-containing agent.
- •Pre-existing neuropathy ≥Grade 2 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.
- •There are additional inclusion criteria. The study center will determine if criteria for participations are met.
研究组 & 干预措施
PF-08046054 Combination Therapy
PF-08046054 + pembrolizumab
干预措施: PF-08046054 (Drug)
PF-08046054 Monotherapy
PF-08046054 monotherapy
干预措施: PF-08046054 (Drug)
PF-08046054 Combination Therapy
PF-08046054 + pembrolizumab
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Number of participants with dose-limiting toxicities (DLTs)
时间窗: Through the first cycle of study treatment; approximately 1 month
Number of participants with DLTs by dose level
时间窗: Through the first cycle of study treatment; approximately 1 month
Number of participants with adverse events (AEs)
时间窗: Through approximately 90 days after last study treatment; up to 3 years
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Number of participants with laboratory abnormalities
时间窗: Through approximately 90 days after last study treatment; up to 3 years
次要结局
- Overall survival (OS)(Up to approximately 3 years)
- Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by investigator assessment(Up to approximately 3 years)
- Duration of objective response (DOR) per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)(Through 30-37 days after last study treatment; up to approximately 3 years)
- Progression-free survival (PFS) per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- PK parameter - Maximum concentration (Cmax)(Through 30-37 days after last study treatment; up to approximately 3 years)
- Incidence of anti-drug antibodies (ADAs)(Through 30-37 days after last study treatment; up to approximately 3 years)
- PK parameter - Trough concentration (Ctrough)(Through 30-37 days after last study treatment; up to approximately 3 years)