A Phase 1/2a, Open-Label, Multicenter, Nonrandomized, Safety and Anti-tumor Activity Study of IMM-1-104, a Novel Oral Dual MEK1/2 Inhibitor in Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 209
- 试验地点
- 17
- 主要终点
- Phase 2a: Overall Response Rate
研究概览
简要总结
This is an open-label, dose-exploration and expansion study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of IMM-1-104 when administered as monotherapy or in combination with approved agents in participants with RAS-mutated or RAS/MAPK activated advanced or metastatic solid tumors. The dose exploration will identify the candidate recommended Phase 2 candidate optimal dose of IMM-1-104 to further explore the anti-tumor activity of IMM-1-104 as monotherapy and in combination with approved agents in multiple Phase 2a proof-of-concept cohorts in malignancies of interest.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Must be ≥18 years of age
- •Must have histologically or cytologically confirmed diagnosis as follows:
- •Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation.
- •Monotherapy Phase 2a: A locally advanced unresectable or metastatic solid tumor malignancies: pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non-small cell lung cancer (NSCLC)
- •Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC
- •Combination therapy Phase 2a, Treatment D: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma with BRAF mutation. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
- •Combination therapy Phase 2a, Treatment E: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
- •Participants must be treatment naive or received prior systemic standard-of-care treatment as follows:
- •Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease
- •Monotherapy Phase 2a:
- •First-line PDAC participants will have received no previous systemic anti-cancer therapy. Second-line PDAC participants will have received no more than one prior systemic anti-cancer therapy.
- •First-line melanoma participants will have received no previous systemic anti-cancer therapy. Second- and third-line participants will have received and failed one or two prior systemic anti-cancer therapies, respectively.
- •NSCLC participants will have received at least one and no more than two previous lines of systemic therapy.
- •Combination therapy (both phases): PDAC participants will have received no previous systemic anti-cancer therapy for their advanced or metastatic disease.
- •Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
排除标准
- •Inability to swallow oral medications
- •Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases
- •History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of serous retinopathy, retinal edema, or retinal pigment epithelial detachment (RPED)
- •Impaired cardiovascular function or clinically significant cardiac disease
- •History of rhabdomyolysis within 3 months prior to start of study treatment
- •Active skin disorder requiring systemic treatment within 3 months prior to the start of study treatment
- •Participants with active, uncontrolled autoimmune disease or participants actively being treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors for management of their autoimmune disease are excluded
- •Receipt of an allogeneic tissue/solid organ transplant
- •Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
研究组 & 干预措施
IMM-1-104 in combination with pembrolizumab (Treatment Group E)
IMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma
干预措施: IMM-1-104 + pembrolizumab (Treatment Group E) (Drug)
IMM-1-104 monotherapy (Treatment Group A)
IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer
干预措施: IMM-1-104 Monotherapy (Treatment Group A) (Drug)
IMM-1-104 in combination with mGnP (Treatment Group B)
IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma
干预措施: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B) (Drug)
IMM-1-104 in combination with mFFX (Treatment Group C)
IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma
干预措施: IMM-1-104 + modified FOLFIRINOX (Treatment Group C) (Drug)
IMM-1-104 in combination with dabrafenib (Treatment Group D)
IMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation
干预措施: IMM-1-104 + dabrafenib (Treatment Group D) (Drug)
结局指标
主要结局
Phase 2a: Overall Response Rate
时间窗: After up to 48 weeks (12 cycles) of study treatment
The proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria
Phase 1: Adverse Events
时间窗: From treatment initiation through 30 days following the last IMM-1-104 dose
Number of participants with adverse events
Phase 1: Dose-Limiting Toxicities
时间窗: The first 21 days of study treatment
Number of participants with dose-limiting toxicities
Phase 1: Recommended Phase 2 Candidate Optimal Dose
时间窗: Initiation of study treatment through 21 days (up to approximately 18 months)
Selection of candidate optimal dose to take forward into Ph2a
次要结局
- Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104(After 12 weeks (3 Cycles) of study treatment)
- Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104(After 12 weeks (3 Cycles) of study treatment)
- Phase 2a: Landmark 3-Month Survival(After 3 months of study participation.)
- Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104(After 12 weeks (3 Cycles) of study treatment)
- Phase 2a: Disease Control Rate (DCR)(After 16 weeks (4 Cycles) of study treatment)
- Phase 2a: Progression Free Survival (PFS)(Up to approximately 2 years)
- Phase 2a: Duration of Response (DOR)(Up to approximately 2 years.)
- Phase 2a: Landmark 6-Month Survival(After 6 months of study participation.)
- Phase 2a: Overall Survival (OS)(Up to approximately 2 Years)