NCT06459869进行中（未招募）1 期
A Multicentre, Open-label, Non-randomized, Phase 1b Trial of NG-350A, a Tumour-selective Anti-CD40-expressing Adenoviral Vector, in Combination With Chemoradiotherapy in Locally Advanced Rectal Cancer (FORTRESS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Akamis Bio
- 入组人数
- 30
- 试验地点
- 18
- 主要终点
- Proportion of patients achieving a response (ncCR / cCR)
研究概览
简要总结
The FORTRESS trial (NG-350A-03) is an open-label, single-arm, and multicentre trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients with locally advanced rectal cancer (LARC) and at least one risk factor for local or distant recurrence.
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
- •Selected Inclusion Criteria:
- •Histologically confirmed adenocarcinoma of the rectum.
- •Locally advanced disease (clinical stage II-III based on pelvic MRI) selected by a multidisciplinary team for treatment with neoadjuvant CRT (which may be followed by CNCT to comprise planned TNT). Patients with oligometastatic disease are permitted provided that the site-specific multidisciplinary team deems them suitable for radical treatment/chemoradiation.
- •Confirmed microsatellite stable (MSS)/proficient mismatch repair (pMMR) status.
- •Provide written informed consent to participate.
- •ECOG Performance Status 0 or
- •Must not be pregnant or breastfeeding.
- •Patients who are sexually active (with either sex) must agree to comply with contraceptive requirements.
- •Adequate lung reserve, renal function, hepatic function, and bone marrow/hematological function assessed ≤ 10 days prior to first dose.
排除标准
- •Recurrent rectal cancer.
- •Distant metastatic disease not amenable to radical treatment/chemoradiation.
- •Other prior malignancy active within the previous 3 years, except for local or organ confined early-stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the trial, including response rate and safety.
- •Splenectomy (patients with prior partial resection remain eligible if the Investigator considers splenic function to not be significantly compromised).
- •Active autoimmune disease that has required systemic therapy in the past 2 years, immunocompromised status in the opinion of the Investigator, or current treatment with systemic immunosuppressive therapy (daily prednisone equivalent for chronic system replacement not to exceed 10mg per day).
- •Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment.
- •Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or thromboembolic event in the last 1 month before the first dose of study treatment.
- •Major surgery in the 14 days before the first dose of study treatment or any surgical wounds that are not fully healed and free of infection or dehiscence.
- •Any prior surgery for rectal cancer or pelvic radiotherapy.
- •Any other anti-cancer or experimental therapy within the previous 12 months or that is planned during the active study treatment period.
- •Treatment with any other enadenotucirev-based virus (parent virus or transgene-modified variants), or anti-CD40 antibody at any time.
- •History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment.
- •Any ongoing Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 coagulation abnormality/coagulopathy.
- •https://www.FortressStudy.org
研究组 & 干预措施
NG-350A plus CRT during a 12-week active study treatment period
Experimental
干预措施: NG-350A IV administration (Drug)
NG-350A plus CRT during a 12-week active study treatment period
Experimental
干预措施: Capecitabine oral administration (Drug)
NG-350A plus CRT during a 12-week active study treatment period
Experimental
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Proportion of patients achieving a response (ncCR / cCR)
时间窗: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)
次要结局
- MRI-based tumor regression grade (mrTRG)(12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT))
- Clinical response (CR) outcome(12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT))
- Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0(1-3 years)
研究者
研究点 (18)
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相关资讯
Akamis Bio's NG-350A Shows 50% Response Rate in Locally Advanced Rectal Cancer Phase 1b Trial- Akamis Bio's NG-350A combined with chemoradiotherapy achieved a 50% composite response rate in the first 10 patients with mismatch repair-proficient locally advanced rectal cancer, doubling the expected 25% rate from standard treatment alone.
- The Phase 1b FORTRESS study demonstrated no serious adverse events related to NG-350A, with the oncolytic immunotherapy designed to drive intratumoral expression of a CD40 agonist antibody.
- Results could enable more patients to pursue organ-preserving "watch-and-wait" protocols instead of life-altering rectal surgery, particularly important as colorectal cancer becomes the leading cause of cancer death in patients under 50.
- The encouraging preliminary data provides clinical proof of concept for NG-350A's potential to advance the standard of care for the approximately 30,000 patients diagnosed annually with this condition in the US.6 months agoFDA Grants Fast Track Designation to NG-350A for Mismatch Repair-Proficient Locally Advanced Rectal Cancer- The FDA has granted fast track designation to NG-350A, an oncolytic immunotherapy developed by Akamis Bio, for treating mismatch repair-proficient locally advanced rectal cancer.
- NG-350A is designed to drive intratumoral expression of a CD40 agonist monoclonal antibody, activating antigen-presenting cells and recruiting T cells to deliver potent anti-tumor immune responses.
- The therapy is being evaluated in the phase 1b FORTRESS trial combining NG-350A with chemoradiotherapy in approximately 30 patients with locally advanced rectal cancer.
- Patients with mismatch repair-proficient tumors represent approximately 90% of locally advanced rectal cancer cases, highlighting a significant unmet medical need for new therapeutic approaches.11 months agoAkamis Bio Initiates Phase 1b FORTRESS Trial of NG-350A for Locally Advanced Rectal Cancer- Akamis Bio has enrolled the first patient in its Phase 1b FORTRESS trial evaluating NG-350A in combination with standard chemoradiotherapy for locally advanced rectal cancer.
- NG-350A is a systemically administered immunotherapy designed to drive intratumoral expression of CD40 agonist antibodies, potentially enhancing immune response against both primary and metastatic tumors.
- The FORTRESS trial builds on promising results from the earlier CEDAR study, which showed significantly higher complete response rates when combining Akamis Bio's immunotherapy with standard chemoradiotherapy.last year