NCT03472560终止2 期
A PHASE 2, OPEN LABEL STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF AVELUMAB (BAVENCIO (REGISTERED)) IN COMBINATION WITH AXITINIB (INLYTA (REGISTERED)) IN PATIENTS WITH ADVANCED OR METASTATIC PREVIOUSLY TREATED NON-SMALL CELL LUNG CANCER OR TREATMENT NAÏVE CISPLATIN-INELIGIBLE UROTHELIAL CANCER JAVELIN MEDLEY VEGF
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 61
- 试验地点
- 34
- 主要终点
- Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR)
研究概览
简要总结
This is a Phase 2 study to evaluate the safety and efficacy of avelumab in combination with axitinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior platinum containing therapy, and in treatment naïve patients with advanced or metastatic urothelial cancer, who are ineligible for cisplatin containing chemotherapy for their advanced disease.
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
- •Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR mutations, ALK or ROS1 translocations/rearrangements where testing is standard of care; received at least 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease (If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy-chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment regimens); Checkpoint inhibitor naïve.
- •Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally advanced or metastatic; No prior systemic treatment for locally advanced or metastatic disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression occurred >12 months after the completion of therapy; Checkpoint inhibitor naïve; Ineligible for receiving cisplatin-containing front-line chemotherapy based at least one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction (defined as creatinine-clearance <60 ml/min); Grade 2 peripheral neuropathy; Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies).
- •At least 1 measurable lesion by RECIST v1.1 not previously irradiated.
- •Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not available, a fresh tumor biopsy must be performed.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •For UC patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)
排除标准
- •Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-GITR, anti-LAG-3, anti-TIM-3 or anti-CTLA-4 antibody (including ipilimumab).
- •Newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids.
- •Radiologically documented evidence of major blood vessel invasion or encasement by cancer or intratumor cavitation, regardless of tumor histology.
- •Active autoimmune disease (that might deteriorate when receiving an immunostimulatory agent).
- •Current use of immunosuppressive medication (except for those listed in protocol).
- •Known prior severe hypersensitivity to the investigational products /monoclonal antibodies.
- •Known history of immune-mediated colitis, inflammatory bowel disease, immune-mediated pneumonitis, pulmonary fibrosis.
- •NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.
研究组 & 干预措施
Avelumab in combination with axitinib
Experimental
Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.
干预措施: Avelumab (MSB0010718C) (Drug)
Avelumab in combination with axitinib
Experimental
Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.
干预措施: Axitinib (AG-013736) (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR)
时间窗: Baseline up to 56 months
ORR: percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) based on investigator's assessment as per Response Evaluation Criteria in Solid Tumours (RECIST version \[v\] 1.1). Both CR and PR were confirmed by repeat assessments performed no less than 4 weeks after criteria for response was first met. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\]10 millimeter \[mm\]). No new lesions. PR was defined as greater than or equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, Progressive Disease.
次要结局
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period(From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months))
- Time to Tumor Response (TTR) in Participants With Confirmed CR or PR(From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months))
- Cmax of Axitinib(Pre-dose, 2 hour post-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15)
- Pre-dose Observed Serum Concentration (Ctrough) of Avelumab(Pre-dose on Cycle 1 Day 1, 15, Cycle 2 Day 1, Cycle 3 Day 15, Cycle 6 Day 15, Cycle 9 Day 15, and Cycle 12 Day 15)
- Ctrough of Axitinib(Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15)
- Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status(Screening, up to 28 days prior to Day 1)
- Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period(From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months))
- Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period(From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months))
- Duration of Response in Participants With Confirmed CR or PR(From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 56 months))
- Overall Survival(From date of start of study treatment until date of death or censoring date (maximum up to 56 months))
- Progression Free Survival (PFS)(From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months))
- Maximum Observed Serum Concentration (Cmax) of Avelumab(Pre-dose, 1 hour post-dose on Cycle 1 Day 1, Day 15 and Cycle 2 Day 1)
- Tumour Mutational Burden (TMB) in Tumor Tissue(Screening, up to 28 days prior to Day 1)
- T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells(Screening, up to 28 days prior to Day 1)
- T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality(Pre-dose on Day 1 of Cycle 1)
- T-cell Receptor (TCR) Sequencing to Identify Total T Cells(Pre-dose on Day 1 of Cycle 1)
- Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab(Within 2 hours pre-dose on Cycle 1 Day 1,15, Cycle 2 Day 1; Day 15 of Cycle 3, 6, 9, 12, end of treatment and 30 days after last dose of study treatment (maximum up to 56 months))
研究者
研究点 (34)
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