Open, Non Controlled, Parallel Cohorts, Multicenter, Phase 2A Study for Evaluation of the Antitumor Activity of GM102 Single Agent and in Combination With Chemotherapy in Patients With Locally Advanced Or Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 5
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Phase 2A study, assessing the antitumor activity and the safety profile of GM102, a new compound (monoclonal antibody), administered alone or in combination with chemotherapy in patients with locally advanced or metastatic colorectal cancer. The primary objective of the study is to evaluate the antitumor activity of GM102 single agent and in combination with trifluridine/tipiracil.
详细描述
GM102 is a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor (fetal receptor mediating the activity of AMH, reexpressed in a variety of solid tumors). GM102 acts through engagement of immune cells (macrophages, natural killer (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of tumor cells.
AMRHII expression was found in 73% of primary colorectal tumors tested.
Advanced/metastatic colorectal cancer (CRC) remains an unmet need disease, with few therapeutic options beyond two or three lines of therapy.
CRC is characterized by a tumor microenvironment (TME) particularly rich in macrophages and more specifically macrophages capable of tumor phagocytosis. The pattern of the TME remains a major prognostic factor in the metastatic setting.
C201 consists in two parallel cohorts and an expansion of cohort II for patients with advanced or metastatic colorectal cancer in two different settings of the disease:
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
- •Histologically confirmed metastatic or locally advanced colorectal adenocarcinoma.
- •Having failed the previous line of treatment for locally advanced or metastatic disease and having received at least two systemic chemotherapy regimens for metastatic colorectal cancer; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion.
- •At least one of the tumor sites amenable to core needle biopsy (may not be the site of disease for measuring antitumor response). Patient must agree to this pre-treatment biopsy and on the principle of a second biopsy under treatment; however, if eventually the second biopsy cannot be performed, patients will continue on the study and will be considered evaluable for efficacy.
- •Available archived CRC tumor tissue sample
- •At least one measurable lesion (superior or equal to 1.0 cm longest diameter or superior or equal to 1.5 cm in short axis for malignant lymph nodes) based on RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 on the screening CT-scan.
- •Written Informed Consent forms signed.
- •Willing and able to comply with the trial requirements.
- •Covered by healthcare insurance in accordance with local requirements.
- •For cohort I (single agent GM102) only: refractory patients, having exhausted all therapeutic options.
- •For cohort II (GM102 in combination with trifluridine/tipiracil) only: patients eligible for trifluridine/tipiracil who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents, regorafenib and anti-Epithelial Growth Factor Receptor (anti-EGFR) agents. Patients must have received at least 2 prior lines of standard chemotherapy for metastatic CRC.
排除标准
- •Age < 18 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status superior or equal to
- •Life expectancy < 12 weeks.
- •Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment.
- •Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.
- •Concurrent treatment with any other anticancer therapy (or investigational agent) or received any anticancer therapy (or investigational agent) within 4 weeks prior to first treatment.
- •Known severe anaphylactic or other hypersensitivity reactions to Investigational Medicinal Product (IMP) and/or its excipients.
- •Unresolved toxicity superior or equal to Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
- •Serious concomitant illness, e.g. active infection requiring systemic antibiotic, antifungal or antiviral drug, or physical examination or laboratory abnormalities, that, in the opinion of the Investigator, would compromise protocol objectives.
- •Poor bone marrow reserve as defined by white blood cell < 3.0 x 10E9/L, neutrophils < 1.5 x 10E9/L or haemoglobin < 9.0 g/dL or platelet count < 100 x 10E9/L.
- •Poor organ function as defined by any one of the following: serum creatinine > 1.5 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN or > 2.5 x ULN if due to Gilbert's syndrome, AST and ALT > 2.5 x ULN in the absence of liver metastasis or > 5 x ULN in case of documented liver metastasis.
- •Severe New York Heart Association (NYHA) III and IV heart failure.
- •Pregnancy or breastfeeding.
- •Patient with reproductive potential who does not agree to use an accepted highly effective method of contraception - per investigator's judgment - during the study period and for at least 6 months following completion of study treatment.
- •Patient deprived of liberty by a judicial or administrative decision, patient admitted to a social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation.
- •Known allergy to rodents.
- •Patients positive to Covid-19
研究组 & 干预措施
Cohort I: GM102 single agent
GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22 of each 28-day cycle
干预措施: GM102 (Drug)
Cohort II: GM102 + trifluridine/tipiracil
GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle
干预措施: GM102 (Drug)
Cohort II: GM102 + trifluridine/tipiracil
GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle
干预措施: Trifluridine/Tipiracil (Drug)
Cohort II expansion: GM102 + trifluridine/tipiracil
GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, after a loading dose of 10 mg/kg q1w during 28-day cycle 1, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle
干预措施: Trifluridine/Tipiracil (Drug)
Cohort II expansion: GM102 + trifluridine/tipiracil
GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, after a loading dose of 10 mg/kg q1w during 28-day cycle 1, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle
干预措施: GM102 expansion (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Through study completion, an average 1 year
ORR from the end of cycle 2 and subsequently confirmed at least 4 weeks later using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Progression Free Survival (PFS) at 6 months
时间窗: 6 months after the first infusion
Proportion of patients without documented progression at 6 months
次要结局
- Incidence of Serious Adverse Event (SAE) and Treatment Emergent Adverse Event (TEAE)(Through study completion, an average 1 year)
- Exposure to murlentamab(At days 1 and 15 of cycles 1, 2 (each cycle is 28 days) and End of Treatment for cohort I and II, an average of one year; days 1, 8,15 and 22 of cycles 1, 2 (each cycle is 28 days) and End of Treatment for cohort II expansion, an average of one year)
- Exposure to trifluridine(At days 1 and 15 of cycles 1, 2 (each cycle is 28 days) and End of Treatment, an average of one year)
- Evidence of anti-murlentamab antibodies (ADA)(Baseline, beginning of every even cycle in pre-dose (each cycle is 28 days) and at the End of Treatment, an average of one year)
- Progression Free Survival (PFS)(Through study completion, an average 1 year)
- Overall Survival (OS)(Through study completion, an average 1 year)
- Immune Overall Response Rate (iORR)(Through study completion, an average 1 year)
- AMHRII (Anti-Mullerian Hormone type II receptor) expression(Up to 2 months)
- Clinical Benefit Rate (CBR)(up to 4 months)
- Tumor Growth Rate (TGR) before and under treatment(up to 2 months)
- Pharmacodynamics evaluation(Up to 2 months)