A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Olomorasib Combination Therapy in Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 13
- 主要终点
- Phase 1: Number of Participants with Adverse Events (AEs) by Severity
研究概览
简要总结
The main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose [RP2CD]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung cancer (NSCLC: the most common type of lung cancer; metastatic: has spread to other parts of the body; KRAS G12C mutant: mutation [change] in the kirsten rat sarcoma viral oncogene homolog [KRAS] gene in tumor cells in which glycine [G] at position 12 is replaced with cystine [C]).
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
- •Participant must have histologically or cytologically confirmed metastatic NSCLC characterized by a KRAS G12C mutation at the time of enrollment. For Phase 1: Participant must have progressed on or after, or have intolerance to, platinum-based chemotherapy and Programmed Death-Ligand 1 (PD-L1)-targeted immunotherapy given in combination or sequentially. Receipt of additional lines of prior therapy is permitted. Progression must have occurred on or after the most recent line of systemic anticancer therapy. For Phase 2: Participant must have progressed on or after platinum-based chemotherapy and PD-L1-targeted immunotherapy given in combination or sequentially. Progression must have occurred on or after the most recent line of systemic anticancer therapy. Receipt of additional lines of prior therapy is not permitted
- •Participant must have at least 1 measurable lesion, according to RECIST version.1.1, that has not been previously irradiated
- •May have brain metastases only if previously definitively, locally treated, and participant is clinically stable and asymptomatic for greater than (>) 2 weeks and is off or receiving low-dose corticosteroid treatment for at least 2 weeks prior to start of study treatment
- •Can have a prior or concurrent second malignancy (other than the disease under study) with natural history or treatment course that is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Participant has history of uncontrolled illness
- •Suspected or known allergies, hypersensitivity, or intolerance to amivantamab excipients or olomorasib excipients
- •Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- •Presence of primary driver mutations (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], mesenchymal-epithelial transition [MET], human epidermal growth factor receptor 2 [HER2], ROS1, neurotrophic tyrosine receptor kinase [NTRK], B-Raf proto-oncogene [BRAF], rearranged during Transfection [RET], neuroblastoma RAS viral oncogene homolog [NRAS], and other KRAS mutations besides G12C) as determined by local genomic testing
- •Prior treatment with any KRAS inhibitor
研究组 & 干预措施
Phase 1: Combination Dose Selection
Participants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments.
干预措施: Amivantamab (Drug)
Phase 2: Expansion
Participants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments.
干预措施: Amivantamab (Drug)
Phase 1: Combination Dose Selection
Participants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments.
干预措施: Olomorasib (Drug)
Phase 2: Expansion
Participants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments.
干预措施: Olomorasib (Drug)
结局指标
主要结局
Phase 1: Number of Participants with Adverse Events (AEs) by Severity
时间窗: Up to approximately 3 years 2 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Up to approximately 3 years 2 months
DLT is defined as drug related adverse events and includes unacceptable non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, or elevations in hepatic enzymes suggestive of drug-induced liver injury of Grade 3 or higher. Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0.
Phase 2: Confirmed Objective Response Rate (ORR)
时间窗: Up to approximately 3 years 2 months
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator review. Confirmatory analysis may be performed using Blinded Independent Central Review (BICR).
次要结局
- Number of Participants with Adverse Events (AEs) by Severity(Up to approximately 3 years 2 months)
- Number of Participants with Abnormalities in Clinical Laboratory Parameters(Up to approximately 3 years 2 months)
- Phase 2: Duration of Response (DoR)(Up to approximately 3 years 2 months)
- Phase 2: Disease Control Rate (DCR)(Up to approximately 3 years 2 months)
- Phase 2: Progression-Free Survival (PFS)(Up to approximately 3 years 2 months)
- Phase 2: Overall Survival (OS)(Up to approximately 3 years 2 months)