A Randomised, Open-label, Multi-centre, Two-arm Phase 3 Study Comparing Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil to Trifluridine/Tipiracil Single Agent With a Safety Lead-In Part in Participants With KRAS/NRAS and BRAF Wild Type Metastatic Colorectal Cancer Previously Treated With Standard Treatment and Anti-EGFR Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 15
- 主要终点
- Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
研究概览
简要总结
This is a randomized phase III study with a safety lead-in part in patients with KRAS/ NRAS and BRAF Wild Type metastatic colorectal cancer who have previously received treatment with oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF agents and anti-EGFR antibodies. The main objective of the safety lead-in part is to assess safety and tolerability of futuximab/modotuximab in combination with trifluridine/tipiracil. The primary objective of the phase III part is to compare Overall Survival of futuximab/modotuximab in combination with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in patients with tumours that are KRAS/NRAS and BRAF wild-type (WT).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically confirmed adenocarcinoma of metastatic colorectal cancer (mCRC), not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumour without RAS (KRAS and NRAS) and BRAF V600E mutations based on Circulating tumour DNA (ctDNA) screening blood test analysis
- •Participants with measurable or non-measurable lesion
- •Participants must have received at least 2 prior regimens of standard chemotherapy for mCRC and had demonstrated progressive disease or intolerance to their last regimen
- •Participants should have received previous treatment with commercially available anti-EGFR mAbs for ≥ 4 months
- •Estimated life expectancy ≥ 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate haematological, renal and hepatic function
排除标准
- •Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman
- •Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part).
- •Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part) or participants who have not recovered from side effects of the surgery
- •Participants with serious/active/uncontrolled infection
- •Known clinically significant cardiovascular disease or condition
- •Significant gastrointestinal abnormality
- •Skin rash of Grade > 1 from prior anti-EGFR at the time of inclusion (Safety Lead-in part) or randomization (Phase 3 part), or any other skin toxicity precluding participation in the study according to investigator's discretion.
- •Treatment with systemic immunosuppressive therapy within 4 weeks prior to inclusion (Safety Lead-in part) or randomization (Phase 3 part)
- •Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part)
- •Patients with other malignancies
研究组 & 干预措施
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)
干预措施: Futuximab/modotuximab (Biological)
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)
干预措施: Trifluridine/Tipiracil (Drug)
Trifluridine/tipiracil (Phase III part)
干预措施: Trifluridine/Tipiracil (Drug)
结局指标
主要结局
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
时间窗: End of cycle 1 (Each cycle is up to 28 days)
DLTs observed during a 28-day period. A DLT is defined as the following: A clinically significant AE graded according to the NCI-CTCAE version 5.0, observed during the initial 28- day treatment period following the first IMP administration. Assessed as unrelated to underlying disease, disease progression, intercurrent illness, or concomitant medications. At least possibly related to the IMPs (futuximab/modotuximab or trifluridine/tipiracil or both) by the investigator and meeting criteria as outlined in the protocol.
Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)
时间窗: up to 4 years 9 months
Time elapsed from date of randomization until the date of death from any cause
次要结局
- Progression Free Survival (Phase III Part)(up to 4 years 9 months)
- Overall Survival (Safety Lead-In Part)(up to 24 months)
- Overall Survival (In Triple Negative) (Phase III Part)(up to 4 years 9 months)
- Adverse Events (Phase III Part)(Through study completion, up to 4 years 9 months)