A Phase 1, First-in-Human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5525 Alone and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 4
- 主要终点
- Primary Efficacy Objectives (Parts 2 and 4)
研究概览
简要总结
This Phase 1, first-in-human (FIH), dose-escalation and dose-expansion study is designed to evaluate the safety, PK, and preliminary anti-tumor activity of VIR-5525 as a monotherapy and in combination with pembrolizumab in participants with solid tumors that are known to express EGFR.
The study will be conducted in the following 4 parts:
- Part 1: VIR-5525 monotherapy dose escalation
- Part 2: VIR-5525 monotherapy dose expansion
- Part 3: VIR-5525 plus pembrolizumab dose escalation
- Part 4: VIR-5525 plus pembrolizumab dose expansion
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
- •Are ≥ 18 years of age, or at the country's legal age of majority of the legal adult age is >18 years, at the time of signing the ICF.
- •Have an ECOG performance status of 0 to
- •Have a life expectancy of at least 12 weeks.
- •Have histological, pathological, or cytological confirmation of disease type that is unresectable, locally advanced, or metastatic.
- •Have measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Have diseases under study, lines of therapy, and biomarker status, as follows:
- •Have one of the following:
- •(Parts 1 and 3): NSCLC (nonsquamous or squamous histology), CRC, HNSCC, or CSCC.
- •Note: Participants with nasopharyngeal tumors are eligible. Note: Participants with upper esophageal or salivary gland tumors are not eligible.
- •Have a solid tumor with EGFR amplification (as previously determined locally with an analytically validated assay in a certified testing laboratory).
- •Have no available standard systemic therapy; or standard therapy is intolerable, not effective, or not accessible; or participant has refused standard therapy.
排除标准
- •Are a WOCBP with a positive serum or urine pregnancy test within 72 hours prior to treatment.
- •Have acute or chronic infections, including the following:
- •Acute or chronic active Epstein-Barr virus (EBV) infection (Exception: asymptomatic EBV-positive participants are still eligible)
- •Chronic active EBV disease defined as a chronic illness lasting at least 6 months, an increased EBV level in either the tissue or the blood, and lack of evidence of a known underlying immunodeficiency
- •History of hepatitis B infection (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) infection (defined as HCV [HCV RNA; qualitative] is detected)
- •History of HIV infection. No HIV testing is required unless mandated by the local health authority.
- •Active infection requiring systemic therapy within 14 days of Cycle 1 Day 1
- •Known positive COVID-19 test result at screening (Exception: If follow-up test is negative, participants may be eligible if asymptomatic and upon consultation with medical monitor)
- •Have a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5525 or pembrolizumab, per the investigator
- •Have a QT interval corrected by Fridericia's method (QTcF) that is >480 ms
- •Have received prior systemic anti-cancer therapy, including investigational agents, within 5 half-lives prior to first dose of study intervention. For drugs with a long t1/2, such as mAbs, or for drugs for which the t1/2 is not known, the last dose should not have been within 28 days prior to first dose of study intervention.
- •Note: If the participant has had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
- •Have received prior radiotherapy within 2 weeks of start of study intervention Note: Participants must have recovered from all radiation-related toxicities to Grade ≤1 or baseline, must not require corticosteroids, and must not have had radiation pneumonitis.
- •Exception: External beam radiotherapy, including palliative external radiation, is allowed.
- •A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Part 1: VIR-5525 Monotherapy Dose Escalation
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.
干预措施: VIR-5525 (Drug)
Part 2: VIR-5525 Monotherapy Dose Expansion
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.
干预措施: VIR-5525 (Drug)
Part 3: VIR-5525 Combination Dose Escalation
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.
干预措施: VIR-5525 (Drug)
Part 3: VIR-5525 Combination Dose Escalation
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
Part 4: VIR-5525 Combination Dose Expansion
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
Part 4: VIR-5525 Combination Dose Expansion
Screening Period: Up to 28 days
Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.
干预措施: VIR-5525 (Drug)
结局指标
主要结局
Primary Efficacy Objectives (Parts 2 and 4)
时间窗: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To evaluate the preliminary anti-tumor activity of VIR-5525 as monotherapy (Part 2) and in combination with pembrolizumab (Part 4) at the recommended dose(s) for expansion cohorts. Endpoint: Objective response, defined as a CR or PR per RECIST v1.1.
Primary Safety Objectives (Parts 1 and 3)
时间窗: From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.
Objective: To evaluate the safety and tolerability of escalating doses of VIR-5525 as monotherapy (Part 1) and in combination with pembrolizumab (Part 3). Endpoint: Incidence and severity of AEs, including DLTs, with severity determined according to NCI CTCAE v5.0, ASTCT CRS, or ASTCT ICANS Consensus Grading, as appropriate.
次要结局
- Secondary Safety Objectives (Parts 1 and 3)(From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.)
- Secondary Efficacy Objectives (Parts 1 and 3)(From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.)
- Secondary Immunogenicity Objectives (Parts 1 Through 4)(From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.)
- Secondary Efficacy Objectives (Parts 2 and 4)(From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.)
- Secondary PK Objectives (Parts 1 Through 4)(From Cycle 1, Day 1 (each cycle is 21 days), up to approximately 52 months.)