A Phase 1 Study of Sigvotatug Vedotin in Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- cisplatin
- 疾病 / 适应症
- Carcinoma, Non-Small Cell Lung
- 发起方
- Seagen, a wholly owned subsidiary of Pfizer
- 入组人数
- 1006
- 试验地点
- 175
- 主要终点
- Number of participants with dose-limiting toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 12天前
概览
简要总结
This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors.
The study will have four parts.
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Part A of the study will find out how much sigvotatug vedotin should be given to participants.
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Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors.
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Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs.
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Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors.
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In Parts C and D, participants will receive sigvotatug vedotin with either:
- Pembrolizumab or,
- Pembrolizumab and carboplatin, or
- Pembrolizumab and cisplatin.
研究者
入排标准
入选标准
- •Disease indication
- •Participants must have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the tumor types listed below (dependent on study part).
- •Non-small cell lung cancer (NSCLC)
- •Head and neck squamous cell cancer (HNSCC)
- •Advanced HER2-negative breast cancer
- •Esophageal squamous cell carcinoma (ESCC)
- •Esophageal/Gastro-esophageal junction adenocarcinoma (EAC/GEJ)
- •Cutaneous squamous cell cancer (cSCC)
- •Exocrine pancreatic adenocarcinoma
- •Bladder cancer
排除标准
- •History of another malignancy within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
- •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 associated with brain metastases for at least 7 days prior to first dose of study drug.
- •In Part D, participants with untreated, asymptomatic CNS metastases smaller than 1 cm may be enrolled without definitive treatment as long as they have no neurological symptoms, no or minimal surrounding edema, and no requirements for corticosteroids.
- •Carcinomatous meningitis
- •Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
- •Pre-existing neuropathy Grade 1 or greater per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) for Parts C and D cohorts with cisplatin or carboplatin; Grade 2 or greater per the NCI CTCAE v5.0 for all other cohorts
- •Any uncontrolled Grade 3 or higher (per NCI CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of sigvotatug vedotin.
研究组 & 干预措施
Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: cisplatin
Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: carboplatin
Part D: sigvotatug vedotin combination therapy in 1L NSCLC
sigvotatug vedotin + pembrolizumab +/- (carboplatin)
干预措施: sigvotatug vedotin
Part D: sigvotatug vedotin combination therapy in 1L NSCLC
sigvotatug vedotin + pembrolizumab +/- (carboplatin)
干预措施: pembrolizumab
Part D: sigvotatug vedotin combination therapy in 1L NSCLC
sigvotatug vedotin + pembrolizumab +/- (carboplatin)
干预措施: carboplatin
Part D: sigvotatug vedotin combination therapy in 1L HNSCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: sigvotatug vedotin
Part D: sigvotatug vedotin combination therapy in 1L HNSCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: pembrolizumab
Part D: sigvotatug vedotin combination therapy in 1L HNSCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: cisplatin
Part D: sigvotatug vedotin combination therapy in 1L HNSCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: carboplatin
Part A: Dose escalation
sigvotatug vedotin monotherapy
干预措施: sigvotatug vedotin
Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: sigvotatug vedotin
Part B: Dose expansion
sigvotatug vedotin monotherapy
干预措施: sigvotatug vedotin
Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC
sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
干预措施: pembrolizumab
结局指标
主要结局
Number of participants with dose-limiting toxicities (DLTs)
时间窗: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Number of participants with adverse events (AEs)
时间窗: Through 30-37 days following last dose of sigvotatug vedotin. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; 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 patients with laboratory abnormalities
时间窗: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
次要结局
- Overall survival (OS)(Up to approximately 3 years)
- Maximum observed concentration (Cmax)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Trough concentration (Ctrough)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Number of participants with antidrug antibodies (ADAs)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Area under the concentration-time curve (AUC)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Concentration at the end of infusion (Ceoi)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Time to maximum observed concentration (Tmax)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
- Duration of objective response (DOR) per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment(Up to approximately 3 years)
- Progression-free survival (PFS) per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- Apparent terminal elimination half-life (t1/2)(Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)