A Phase 1a/1b Study of COM701 as Monotherapy and In Combination With an Anti-PD-1 Antibody in Subjects With Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Compugen Ltd
- 入组人数
- 121
- 试验地点
- 11
- 主要终点
- Determine the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDFE) (COM701 monotherapy and in combination with nivolumab).
研究概览
简要总结
This is a Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary clinical activity of COM701 as monotherapy and in combination with nivolumab.
详细描述
This Phase 1 study evaluates the safety, tolerability, Pharmacokinetics (PK) and preliminary clinical activity of COM701 an inhibitor of poliovirus receptor related immunoglobulin domain containing (PVRIG) as monotherapy and in combination with nivolumab in subjects with advanced solid tumors. Cohort expansion will be explored evaluating COM701 monotherapy and in combination with nivolumab in subjects with the following select tumor types (Non-Small cell lung cancer (NSCLC), Ovarian, Breast (including Triple negative breast cancer (TNBC) and endometrial cancer. Other tumor types such as CRC-MSS, CRC-KRAS mutant will be enrolled based on emerging clinical activity data.
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
- •Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Subjects who received prior immune-stimulatory antitumor agents, such as anti-PD-1, anti-PD-L1, anti-CTLA-4, OX-40, CD137, etc. are eligible.
- •Histologically or cytologically confirmed, locally advanced or metastatic solid malignancy and has exhausted all the available standard therapy or is not a candidate for the available standard therapy.
- •Select Tumor Types (COM701 monotherapy cohort expansion; COM701 in combination with nivolumab):
- •Breast cancer (TNBC): Histologically confirmed incurable, advanced estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) adenocarcinoma of the breast, as defined by the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines. Disease recurrence or progression during or after at least one systemic treatment that included an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. Subjects must have progressed after a poly ADP-ribose polymerase (PARP) inhibitor for patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutated metastatic breast cancer. P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
- •Endometrial cancer: Subjects with locally advanced or metastatic endometrial cancer, disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy. P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
- •Ovarian cancer: Disease recurrence or progression during or after prior therapy that included: surgical resection, platinum agent, PARP inhibitor (for subjects with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer or as a maintenance therapy for subjects who have had complete or partial response to platinum-based therapy). P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
- •NSCLC: Documented stage IIIB or IV or recurrent NSCLC, Disease recurrence or progression during or after prior treatment that included: platinum agent, targeted therapy such as a TKI (if with biopsy-confirmed cytogenetic mutation eg EGFR, ROS, BRAF). COM701 monotherapy expansion cohort.
- •CRC (microsatellite stable, KRAS mutation) - P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
- •For Phase 1a monotherapy expansion and Phase 1b only: subject has at least one measurable lesion that could be followed during the study according to RECIST v1.
排除标准
- •Active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose of COM
- •Symptomatic interstitial lung disease or inflammatory pneumonitis.
- •History of immune-related events that lead to immunotherapy treatment discontinuation.
- •Untreated or symptomatic central nervous system (CNS) metastases.
- •Impaired cardiac function or clinically significant cardiac disease, including any of the following: a) Unstable angina pectoris ≤ 6 months prior to first scheduled dose of COM701; b) Acute myocardial infarction ≤ 6 months prior to first scheduled dose of COM701.
研究组 & 干预措施
P1b (Combination Cohort Dose Expansion).
COM701 administered IV every 4 weeks in combination with Opdivo (Nivolumab) 480 mg administered IV every 4 weeks. Cohort expansion in subjects with the following select tumor types (Breast, Ovarian, Endometrial and Colorectal cancer).
干预措施: COM701 with Opdivo (Nivolumab). (Drug)
P1a Arm A (Monotherapy Dose Escalation).
COM701 monotherapy sequential dose escalation administered IV every 3 weeks and a Cohort IV every 4 weeks. Up to 8 dose escalation cohorts may be evaluated until a maximum tolerated dose or recommended phase 2 dose is identified.
干预措施: COM701 (Drug)
P1a Arm B (Combination Dose Escalation).
COM701 sequential dose escalation administered IV every 3 weeks in combination with Opdivo (Nivolumab) 360mg administered IV every 3 weeks and COM701 administered IV every 4 weeks in combination with Opdivo (Nivolumab) 480mg administered IV every 4 weeks.
干预措施: COM701 with Opdivo (Nivolumab). (Drug)
P1a Arm A (Monotherapy Expansion).
COM701 monotherapy administered IV every 4 weeks. Cohort expansion in subjects with the following select tumor types (NSCLC, Breast, Ovarian, Endometrial and Colorectal cancer).
干预措施: COM701 (Drug)
结局指标
主要结局
Determine the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDFE) (COM701 monotherapy and in combination with nivolumab).
时间窗: Approximately 2 year.
Incidence of subjects with Adverse Events (AEs) as per CTCAE v4.03 and Dose-Limiting Toxicities (DLTs).
时间窗: DLT evaluation window in the 1st cycle (21 or 28 days).
To evaluate the safety profile of COM701 monotherapy and in combination with nivolumab.
次要结局
- Overall Response Rate as per RECIST v1.1(Approximately 2 years.)
- Incidence of subjects with Anti-COM701 antibody.(Approximately 2 years.)