NCT06118086招募中1 期
A Phase 1/2, Multicenter, Open-label Study of REM-422, a MYB mRNA Degrader, in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma
Remix Therapeutics9 个研究点 分布在 2 个国家目标入组 125 人开始时间: 2023年12月20日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 125
- 试验地点
- 9
- 主要终点
- Frequency and severity of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with advanced Adenoid Cystic Carcinoma (ACC)
详细描述
This is a Phase 1/2, open-label, non-randomized, multicenter study investigating REM-422, a potent, selective, and oral small molecule mRNA degrader that reduces expression of the MYB transcription factor for patients with recurrent, metastatic, or unresectable ACC.
This study includes a Dose Escalation Phase and a Confirmatory Cohort phase. The purpose of the Dose Escalation Phase is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REM-422 in patients with recurrent or metastatic ACC. The purpose of the Confirmatory Cohort is to further evaluate the safety and anti-tumor activity of the RP2D carried forward from Dose Escalation in patients with recurrent, metastatic, or unresectable ACC.
Participation in this study will continue until disease progression, therapy intolerance, or participant withdrawal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Be able to provide informed consent.
- •Be 18 years or older at the time of informed consent.
- •Disease criteria:
- •Histologically confirmed ACC, any site of origin.
- •Dose Escalation phase ONLY:
- •Have locally advanced or metastatic ACC
- •Evidence of radiographic progression and/or signs and symptoms associated with their disease (eg, pain, dyspnea, reduced performance status). Participants who have stable disease while being treated with another agent that is not tolerated are eligible after the appropriate washout period.
- •Confirmatory Cohort phase ONLY:
- •Have metastatic, recurrent, or unresectable ACC
- •Measurable disease at the time of enrollment. At least 1 measurable lesion according to RECIST v1.1 criteria. Participants must have radiographic evidence of disease progression by RECIST v1.1 criteria ≤ 6 months prior to study enrollment. Radiographic eligibility as determined by Central IUO assay.
- •MYB poison exon biomarker positive tumor(s) confirmed by central IUO assay.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Tumor Tissue Requirements
- •Dose Escalation Phase ONLY: be able to provide during Screening a tissue specimen of either a fresh biopsy of a non-target lesion or an archival tumor sample obtained within the last 6 years. A formalin-fixed paraffin-embedded (FFPE) block can be submitted or a minimum of 15 freshly sectioned unstained slides. Agree to an on-treatment biopsy to be obtained ~4-8 weeks after initiation of REM-422 unless medically contraindicated.
- •Confirmatory Cohort phase ONLY: be able to provide, during Pre-Screening, a tissue specimen of either a fresh biopsy of non-targetable lesion or an archival tumor sample obtained within the last 6 years that is interpretable for the biomarker positivity. An FFPE block can be submitted or a minimum of 15 fresh sectioned unstained slides.
- •At least 3 weeks since prior systemic non-investigational therapy at the time of start of REM-
- •Toxicities from prior therapy must be stable or recovered to ≤ Grade
- •Note: Stable chronic and clinically non-significant conditions (≤ Grade 2) that are not expected to resolve are exceptions (eg, neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies, etc.), and patients with these conditions may enroll.
- •Participants must be able to swallow and retain oral medications.
- •Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
- •Participants of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
- •Participants Of Child Bearing Potential must agree to use acceptable, effective methods of contraception as outlined in Appendix 1 and not donate ova from Screening until 6 months after discontinuation of REM-
- •Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
- •Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-
- •Adequate bone marrow, organ function and laboratory parameters
排除标准
- •Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
- •Clinically significant active infection. Simple urinary tract infection, uncomplicated bacterial pharyngitis responding to active treatment are permitted. Participants receiving intravenous antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals or antifungals are permitted).
- •Evidence of active HIV infection.
- •Evidence of currently active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Primary immunodeficiency.
- •Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent. Topical or inhaled corticosteroids with minimal systemic absorption may enroll and continue minimal corticosteroids if the participant is on a stable dose.
- •Live vaccine ≤ 6 weeks prior to the start of REM-
- •Use of strong CYP3A inhibitors or CYP3A inducers
- •Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (e.g., omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study
- •Pregnancy or participants planning to become pregnant during the duration of the study, or lactation.
- •Participants with malabsorption syndrome, a disease significantly affecting gastrointestinal function, or resection of the stomach or bowel.
- •Current use of prohibited medication ≤ 1 week before starting REM-
- •Clinically significant cardiovascular disease:
- •Participants who have undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, meninges, or surgical procedures requiring general anesthesia) < 4 weeks prior to enrollment.
- •History of organ transplant that requires use of immunosuppressive agents.
- •History or current autoimmune disease (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
- •Radiation therapy ≤ 7 days prior to the start of REM-
- •Concurrent or previous other malignancy (other than adenoid cystic carcinoma, hematologic malignancies, or primary central nervous system [CNS] malignancies) ≤ 2 years of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix.
- •Participants receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.
- •Unwillingness or inability to follow protocol requirements.
- •Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.
研究组 & 干预措施
REM-422
Experimental
- Dose Escalation: Participants will receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)-422, oral capsule administered once daily
- Ph 2 Confirmatory Cohort: Participants will receive REM-422 at the identified RP2D
- Treatment will continue until disease progression, therapy intolerance, or participant withdrawal
- Safety evaluation will continue until 30 days of last administration of REM-422
干预措施: REM-422 (Drug)
结局指标
主要结局
Frequency and severity of Treatment Emergent Adverse Events (TEAEs)
时间窗: 18 months
Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and number of participants with Dose Limiting Toxicities will be assessed to determine Safety and Tolerability of REM-422
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
时间窗: Assessed at the end of Cycle 1 for each participant
Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and the number of participants with Dose Limiting Toxicities will be assessed
Overall Response Rate (ORR) in Phase 2 Confirmatory Cohort
时间窗: 18 months
ORR will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 following treatment with REM-422
次要结局
- Time to Response (mTTR)(18 months)
- Median Overall Survival (mOS)(18 months)
- Determine pharmacokinetic profile (Cmax) of REM-422(18 months)
- Determine pharmacokinetic profile (Cmin) of REM-422(18 months)
- Determine pharmacokinetic profile (Tmax) of REM-422(18 months)
- Determine pharmacokinetic profile (AUC) of REM-422(18 months)
- Duration of Response (DoR)(18 months)
- Overall Response Rate (ORR)(18 months)
- Median Progression Free Survival (mPFS)(18 months)
- Duration of Response (DoR)(18 months)
- Time to Response (mTTR)(18 months)
- Disease Control Rate (DCR)(6 months)
- Median Overall Survival (mOS)(18 months)
- Determine pharmacokinetic profile (Cmax) of REM-422(18 months)
- Determine pharmacokinetic profile (Cmin) of REM-422(18 months)
- Determine pharmacokinetic profile (Tmax) of REM-422(18 months)
- Determine pharmacokinetic profile (AUC) of REM-422(18 months)
- Median Progression Free Survival (mPFS)(6 months, 12 months)
研究者
研究点 (9)
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相关资讯
FDA Grants Fast Track Designation to Remix Therapeutics' REM-422 for Adenoid Cystic Carcinoma Treatment- The FDA has granted Fast Track designation to REM-422, a first-in-class oral small molecule MYB mRNA degrader developed by Remix Therapeutics for treating recurrent, metastatic or unresectable adenoid cystic carcinoma.
- Preliminary Phase 1 results demonstrate strong anti-tumor activity and favorable safety profile in patients whose tumors express MYB transcripts containing a poison exon.
- The designation addresses a critical unmet medical need, as there are currently no approved treatment options for patients with MYB-driven adenoid cystic carcinoma.
- REM-422 represents a novel therapeutic approach targeting MYB, a key oncogenic driver that has historically been difficult to drug through traditional methods.6 months agoRNA-Targeting Small Molecules Emerge as New Frontier in Drug Discovery with Major Pharma Partnerships- Remix Therapeutics secured major partnerships with Johnson & Johnson ($45M upfront, potential $1B+) and Roche ($30M upfront, $1.12B in milestones) for RNA-targeting small molecule development.
- The company's lead candidate REM-422 is advancing through Phase I trials for adenoid cystic carcinoma and acute myeloid leukemia by targeting the oncogenic transcription factor MYB.
- Skyhawk Therapeutics' RNA-splicing modulator SKY-0515 demonstrated clinical improvement in Huntington's disease patients and is now in Phase II/III trials.
- RNA-targeting approaches could vastly expand druggable targets since 80% of human DNA is converted to RNA compared to only 1% made into protein.7 months ago