Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 167
- 试验地点
- 36
- 主要终点
- Part 1a/b (Cohorts A and B): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
研究概览
简要总结
This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For All Cohorts:
- •Adult ≥ 18 years old.
- •Metastatic disease not amenable to potentially curative surgery and with available archival tumor tissue or fresh tumor tissue biopsy.
- •Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Adequate bone marrow and organ function per defined criteria in the protocol.
- •Recovered from acute laboratory and clinical toxicities of prior anti cancer treatment to NCI CTCAE v5.0 grade ≤1 at time of screening, except alopecia and amenorrhea.
- •For Cohort A:
- •First line metastatic colorectal adenocarcinoma.
- •For Cohort B:
- •Second line metastatic colorectal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.
- •For Cohort C:
- •Second line metastatic gastroesophageal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease, and which must include a platinum agent and fluoropyrimidine doublet.
- •For Cohort D:
- •Second or third line metastatic renal cell carcinoma with a clear cell component and has received one or two lines of treatment for metastatic disease that included an anti angiogenic agent for at least 4 weeks with radiologic progression on that treatment.
- •For subjects starting from Part 1a in Cohorts A and B:
- •Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).
- •Not requiring immediate initiation of anti cancer therapy per investigator's best judgement.
- •For subjects starting from Part 2 in Cohort C:
- •Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).
排除标准
- •For All Cohorts:
- •Currently receiving any of the prohibited medications or has contraindications as outlined in the 'Contraindications' to SOC regimen components.
- •Symptomatic brain metastases or brain metastases that require directed therapy (such as focal radiotherapy or surgery).
- •Suspected or proven immunocompromised state, or infections (as defined in the protocol).
- •Conditions that have a high risk of clinically significant bleeding after administration of anti VEGF agents.
- •Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular disease.
- •For Cohort D:
- •Concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/
- •Impairment of GI function or GI disease that may significantly alter the absorption of cabozantinib.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Cohort D: 2nd or 3rd line renal cell carcinoma
Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
干预措施: Cabozantinib (Drug)
Cohort A: 1st line colorectal cancer
Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
干预措施: Gevokizumab (Drug)
Cohort A: 1st line colorectal cancer
Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
干预措施: Bevacizumab (Drug)
Cohort A: 1st line colorectal cancer
Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab
干预措施: Modified FOLFOX6 (Drug)
Cohort B: 2nd line colorectal cancer
Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
干预措施: Gevokizumab (Drug)
Cohort B: 2nd line colorectal cancer
Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
干预措施: Bevacizumab (Drug)
Cohort B: 2nd line colorectal cancer
Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab
干预措施: FOLFIRI (Drug)
Cohort C: 2nd line gastroesophageal cancer
Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
干预措施: Gevokizumab (Drug)
Cohort C: 2nd line gastroesophageal cancer
Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
干预措施: Ramucirumab (Drug)
Cohort C: 2nd line gastroesophageal cancer
Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab
干预措施: Paclitaxel (Drug)
Cohort D: 2nd or 3rd line renal cell carcinoma
Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib
干预措施: Gevokizumab (Drug)
结局指标
主要结局
Part 1a/b (Cohorts A and B): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
时间窗: Baseline, Day 15
Log scale change of hs-CRP at Day 15 from baseline
Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]
时间窗: First 4 weeks of combination treatment
DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]
时间窗: First 6 weeks of combination treatment
DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]
时间窗: At 15 months
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]
时间窗: At 9 months
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]
时间窗: At 6 months
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
次要结局
- Overall response rate (ORR) per investigator assessment using RECIST v1.1(Up to 5 years)
- Duration of response (DOR) per investigator assessment using RECIST v1.1(Up to 5 years)
- Disease Control Rate (DCR) per investigator assessment using RECIST v1.1(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level](Up to 5 years)
- PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)(Up to 5 years)
- Number of patients with anti-drug antibodies for gevokizumab in the combination regimens(Up to 5 years)