A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Optimization Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of KQB365 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies With KRAS G12S or G12C Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 20
- 主要终点
- Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1)
研究概览
简要总结
The goal of this clinical trial is to learn if KQB365 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB365. The main questions it aims to answer are:
- What is the safe dose of KQB365 by itself, in combination with cetuximab, or in combination with KQB198?
- Does KQB365 alone, in combination with cetuximab, or in combination with KQB198 decrease the size of the tumor?
- What happens to KQB365 in the body?
Participants will:
- Receive KQB365 infusion weekly alone, in combination with cetuximab, or in combination with oral KQB198.
- Visit the clinic about 9 times in the first 6 weeks, and then once every week after that.
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
- •PART 1 (monotherapy and combo therapy with KQB198): Histologically confirmed diagnosis of a solid tumor malignancy with either a KRAS G12C or KRAS G12S mutation.
- •PART 1 (combo therapy with Cetuximab) & PART 2: Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with either a KRAS G12C or KRAS G12S mutation.
- •Unresectable or metastatic disease
- •No available treatment with curative intent
- •Adequate organ function
- •Measurable disease per RECIST v1.1
排除标准
- •Active primary central nervous system tumors
- •Cardiac abnormalities
- •Active interstitial lung disease
- •Unable to swallow or GI condition that prevents absorption for patients in KQB198 combination cohorts
研究组 & 干预措施
Monotherapy Dose Escalation (Part 1)
Drug: KQB365
- Intravenous KQB365
干预措施: KQB365 (Drug)
Combo Therapy with Cetuximab Dose Escalation (Part 1)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: KQB365 (Drug)
Combo Therapy with Cetuximab Dose Escalation (Part 1)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: Cetuximab (Drug)
Monotherapy Dose Expansion - RP2D (Part 2)
Drug: KQB365
- Intravenous KQB365
干预措施: KQB365 (Drug)
Monotherapy Dose Expansion - RP2D-1 (Part 2)
Drug: KQB365
- Intravenous KQB365
干预措施: KQB365 (Drug)
Combo Therapy with Cetuximab Dose Expansion - RP2D (Part 2)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: KQB365 (Drug)
Combo Therapy with Cetuximab Dose Expansion - RP2D (Part 2)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: Cetuximab (Drug)
Combo Therapy with Cetuximab Dose Expansion - RP2D-1 (Part 2)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: KQB365 (Drug)
Combo Therapy with Cetuximab Dose Expansion - RP2D-1 (Part 2)
Drug: KQB365 - Intravenous KQB365
Drug:
- Intravenous cetuximab
干预措施: Cetuximab (Drug)
Combo Therapy with KQB198 Dose Escalation (Part 1)
Drug: KQB365 - Intravenous KQB365
Drug:
- Oral KQB198
干预措施: KQB365 (Drug)
Combo Therapy with KQB198 Dose Escalation (Part 1)
Drug: KQB365 - Intravenous KQB365
Drug:
- Oral KQB198
干预措施: KQB198 (Drug)
结局指标
主要结局
Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1)
时间窗: From enrollment to the end of treatment
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, SAEs, and DLTs, from first dose of study treatment to 30 days after last dose of study treatment.
Recommended Phase 2 Dose (RP2D) (Part 1)
时间窗: up to 35 months
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D.
Efficacy and Optimal Biologic Dose of study treatment, as measured by Objective Response Rate (ORR) (Part 2)
时间窗: up to 35 months
ORR is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of study treatment until last dose.
次要结局
- Concentration-time curve (AUC)(up to 35 months)
- Maximum plasma concentration (Cmax)(up to 35 months)
- Time to maximum plasma concentration (tmax)(up to 35 months)
- Overall survival (OS)(up to 35 months)
- Progression-free survival (PFS)(up to 35 months)
- Overall response rate (ORR)(up to 35 months)
- Duration of response (DOR)(up to 35 months)
- Time to response (TTR)(up to 35 months)
- Disease control rate (DCR)(up to 35 months)