PHASE 1B/2 STUDY OF PF-04136309 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA

The purpose of this Phase 1b/2 study is to evaluate the safety and tolerability of PF-04136309 in combination with nab-paclitaxel and gemcitabine, characterize the dose-limiting toxicities (DLTs) and overall safety profile of escalated doses of PF-04136309 and the associated schedule, determine the maximum tolerated dose (MTD), and to assess the enhancement of efficacy of PF-04136309 in combination with nab-paclitaxel and gemcitabine versus nab-paclitaxel + gemcitabine + placebo in terms of Progression Free Survival.

开始日期2016-05-04

申办/合作机构

Pfizer Inc.

NCT02598206 / Completed临床1期

A Phase 1, Randomized, Open Label, Single Dose, 2-period Crossover Study To Evaluate Food Effect On The Pharmacokinetics Of Pf-04136309 In Healthy Subjects

The purpose of this study is to evaluate the effect of food intake on PF-04136309 pharmacokinetics (PK) following a single dose at 1000 mg.

开始日期2015-12-01

申办/合作机构

Pfizer Inc.

NCT01413022 / Completed临床1期IIT

Phase IB Study of FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

This phase I trial studies the side effects and optimal dose of PF-04136309 when given with combination chemotherapy (FOLFIRINOX; 5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in treating patients with locally advanced or borderline resectable pancreatic cancer. These patients are not candidates for surgical resection which is the most effective treatment for pancreatic cancer. Giving PF-04136309 together with FOLFIRINOX may shrink pancreatic tumors in some patients so that surgery becomes an option

开始日期2012-04-01

申办/合作机构

Washington University School of Medicine

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100 项与 PF-4136309 相关的专利（医药）

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项与 PF-4136309 相关的文献（医药）

2021-01-01·Journal of Cancer3区 · 医学

GOLM1 Drives Colorectal Cancer Metastasis by Regulating Myeloid-derived Suppressor Cells

3区 · 医学

ArticleOA

作者: Dang, Yunzhi ; Zhao, Shuhong ; Cao, Ximing ; Yu, Jiao ; Jin, Long ; Wang, Qing

Colorectal cancer (CRC) is the most common digestive neoplasms worldwide, metastasis and recurrence still account for the leading cause for the high mortality rate, but the exact mechanisms remain unclear. More and more evidence has indicated that the deregulation of GOLM1 plays a crucial role in cancer progression. Here, we reported a novel role of GOLM1 in promoting CRC metastasis. In this study, the expression of GOLM1 was detected in human CRC cohort. The function of GOLM1 in CRC metastasis was analyzed by in vivo cecum orthotopic model. We found that the expression of GOLM1 was significantly increased in CRC tissues than adjacent nontumor. Overexpression GOLM1 can promote CRC immune escape and metastasis by recruiting of myeloid-derived suppressor cells (MDSCs) at the same time. PF-04136309, a small molecule and specific inhibitor of CCR2 can largely suppressed GOLM1-mediated CRC metastasis. These results suggest that GOLM1 can promote CRC metastasis and is a prognostic biomarker in human CRC.

2020-06-01·Investigational New Drugs

Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma

Article

作者: Ganguly, Bishu ; Belt, Brian A ; Joh, Tenshang ; Jacobs, Ira A ; Taylor, Carrie T ; Britten, Carolyn D ; Noel, Marcus ; Gamelin, Eric C ; Linehan, David C ; Wolpin, Brian M ; Yin, Donghua ; O'Reilly, Eileen M ; Ryan, David P ; Lowery, Maeve A ; Bullock, Andrea J

SummaryBackground In pancreatic ductal adenocarcinoma (PDAC), the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) axis plays a key role in immunosuppressive properties of the tumor microenvironment, patient prognosis, and chemoresistance. This phase Ib study assessed the effects of the orally administered CCR2 inhibitor PF-04136309 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic PDAC. Methods Patients received PF-04136309 twice daily (BID) continuously plus nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) administered on days 1, 8, and 15 of each 28-day cycle. The primary objectives were to evaluate safety and tolerability, characterize dose-limiting toxicities (DLTs), and determine the recommended phase II dose (RP2D) of PF-04136309. Results In all, 21 patients received PF-04136309 at a starting dose of 500 mg or 750 mg BID. The RP2D was identified to be 500 mg BID. Of 17 patients treated at the 500 mg BID starting dose, three (17.6%) experienced a total of four DLTs, including grade 3 dysesthesia, diarrhea, and hypokalemia and one event of grade 4 hypoxia. Relative to the small number of patients (n = 21), a high incidence (24%) of pulmonary toxicity was observed in this study. The objective response rate for 21 patients was 23.8% (95% confidence interval: 8.2–47.2%). Levels of CD14 + CCR2+ inflammatory monocytes (IM) decreased in the peripheral blood, but did not accumulate in the bone marrow. Conclusions PF-04136309 in combination with nab-paclitaxel plus gemcitabine had a safety profile that raises concern for synergistic pulmonary toxicity and did not show an efficacy signal above nab-paclitaxel and gemcitabine. ClinicalTrials.gov identifier: NCT02732938.

2016-05-01·The Lancet Oncology1区 · 医学

Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial

1区 · 医学

Article

作者: Strasberg, Steven M ; Belt, Brian A ; Fields, Ryan C ; Linehan, David C ; Wang-Gillam, Andrea ; Toriola, Adetunji T ; Tan, Benjamin R ; Goedegebuure, S Peter ; Yano, Motoyo ; Panni, Roheena Z ; Nywening, Timothy M ; Lockhart, A Craig ; Lim, Kian-Huat ; Cusworth, Brian M ; Hawkins, William G ; DeNardo, David G ; Worley, Lori A ; Fowler, Kathryn J ; Nieman, Rebecca K ; Sanford, Dominic E ; Suresh, Rama

BACKGROUNDIn pancreatic ductal adenocarcinoma, the CCL2-CCR2 chemokine axis is used to recruit tumour-associated macrophages for construction of an immunosuppressive tumour microenvironment. This pathway has prognostic implications in pancreatic cancer, and blockade of CCR2 restores anti-tumour immunity in preclinical models. We aimed to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX chemotherapy (oxaliplatin and irinotecan plus leucovorin and fluorouracil).METHODSWe did this open-label, dose-finding, non-randomised, phase 1b study at one centre in the USA. We enrolled treatment-naive patients aged 18 years or older with borderline resectable or locally advanced biopsy-proven pancreatic ductal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1, and normal end-organ function. Patients were allocated to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), and bolus fluorouracil 400 mg/m(2), followed by 2400 mg/m(2) 46-h continuous infusion), administered every 2 weeks for a total of six treatment cycles, or in combination with oral PF-04136309, administered at a starting dose of 500 mg twice daily in a standard 3 + 3 dose de-escalation design. Both FOLFIRINOX and PF-04136309 were simultaneously initiated with a total treatment duration of 12 weeks. The primary endpoints were the safety, tolerability, and recommended phase 2 dose of PF-04136309 plus FOLFIRINOX, with an expansion phase planned at the recommended dose. We analysed the primary outcome by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01413022.RESULTSBetween April 19, 2012, and Nov 12, 2014, we treated 47 patients with FOLFIRINOX alone (n=8) or with FOLFIRINOX plus PF-04136309 (n=39). One patient had a dose-limiting toxic effect in the dose de-escalation group receiving FOLFIRINOX plus PF-04136309 at 500 mg twice daily (n=6); this dose was established as the recommended phase 2 dose. We pooled patients in the expansion-phase group (n=33) with those in the dose de-escalation group that received PF-04136309 at the recommended phase 2 dose for assessment of treatment-related toxicity. Six (75%) of the eight patients receiving FOLFIRINOX alone were assessed for treatment toxicity, after exclusion of two (25%) patients due to insurance coverage issues. The median duration of follow-up for treatment toxicity was 72·0 days (IQR 49·5-89·0) in the FOLFIRINOX alone group and 77·0 days (70·0-90·5) in the FOLFIRINOX plus PF-04136309 group. No treatment-related deaths occurred. Two (5%) patients in the FOLFIRINOX plus PF-04136309 group stopped treatment earlier than planned due to treatment-related toxic effects. Grade 3 or higher adverse events reported in at least 10% of the patients receiving PF-04136309 included neutropenia (n=27), febrile neutropenia (n=7), lymphopenia (n=4), diarrhoea (n=6), and hypokalaemia (n=7). Grade 3 or higher adverse events reported in at least 10% of patients receiving FOLFIRINOX alone were neutropenia (n=6), febrile neutropenia (n=1), anaemia (n=2), lymphopenia (n=1), diarrhoea (n=2), hypoalbuminaemia (n=1), and hypokalaemia (n=3). Therapy was terminated because of treatment-related toxicity in one (17%) of the six patients receiving FOLFIRINOX alone. 16 (49%) of 33 patients receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective tumour response, with local tumour control achieved in 32 (97%) patients. In the FOLFIRINOX alone group, none of the five patients with repeat imaging achieved an objective response, although four (80%) of those patients achieved stable disease.INTERPRETATIONCCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable.FUNDINGWashington University-Pfizer Biomedical Collaborative.

项与 PF-4136309 相关的新闻（医药）

2024-08-11

·佰傲谷BioValley

错综复杂的趋化因子

趋化因子系统参与调节细胞迁移、粘附、定位和细胞间相互作用，作用于肿瘤细胞和免疫细胞调节二者细胞活动，高度参与肿瘤的发展过程。根据肿瘤发生过程中所处的阶段、免疫细胞的活化状态、效应与调控反应间的平衡以及趋化因子受体在效应靶细胞和调节性靶细胞上的相对表达，趋化因子会表现出促肿瘤和抗肿瘤两种效应，甚至同一趋化因子作用于不同细胞，具有两种截然相反的效应。一、促瘤趋化因子 1. CCL2：通过CCL2-CCR2轴募集肿瘤相关免疫抑制细胞；介导肿瘤与肿瘤相关巨噬细胞（TAM）相互作用，提高肿瘤干细胞特性、转移能力和治疗抵抗。 2. CXCL1/CXCL8：通过CXCL1/CXCL8-CXCR2轴募集肿瘤相关免疫抑制细胞。 3. CXCL12：通过CXCR4-CXCL12轴促进TAM分化为血管周围TAM细胞，提高血管通透性，使肿瘤细胞向血管内浸润；实体瘤增加骨髓基质细胞中CXCL12的表达，导致表达CXCR4的髓样细胞积聚，影响免疫细胞的发育成熟，CXCR4-CXCL12轴参与Treg向骨髓的迁移。 4. CCR4：在肿瘤微环境（TME）中募集调节性T细胞（Treg）。 5. CCR6：促进Treg细胞在TME原位增殖。 6. CCR8：在TME内DC细胞附近募集Treg，并通过抗原识别使Treg具有免疫抑制作用；通过CCR8-CCL1轴增加Foxp3表达维持Treg细胞的免疫抑制能力。 7. CCR4+Th2、CCR6+Th17、CXCR3+Th1、CXCR5+Tfh，以上4类趋化因子受体分别在不同细胞中的表达，与Treg抑制功能有一定相关性。二、抗瘤趋化因子 1. XCL1：通过XCL1-XCR1轴介导cDC1细胞向肿瘤募集，促进cDC1与CD8+T细胞相互作用，促使T细胞扩增和获得效应器功能。 2. CXCL11：其表达与髓源性抑制细胞（MDSCs）的丰度和CD8+T细胞浸润程度成反比。 3. CCR7：介导cDC1和cDC2细胞从肿瘤向TDLN迁移，启动T细胞的效应功能。 4. CCL21：介导T细胞和DC细胞向肿瘤引流淋巴结（TDLN）募集，其表达减少会影响免疫细胞群定位，最终可能导致T细胞活性降低。 5. CX3CR1：CD8+T细胞接收到CX3CR1信号才能发挥抗肿瘤作用。三、双效趋化因子 1. CCR5：CCR5-CCL5轴介导cDC1向肿瘤募集，能同时募集Treg细胞和CD8+T细胞；调控TAM表型和功能，介导肿瘤与TAM相互作用，提高肿瘤肝细胞性、转移能力、治疗抵抗 2. CXCR3：CXCR3-CXCL9/CXCL10轴也能同时募集Treg和CD8+T细胞；使干细胞样TCF-1+细胞向cDC1细胞募集、在TME中重激活和通过接触IL-2获得效应器功能；调控免疫效应细胞在肿瘤附近的定位。四、药物开发一些趋化因子的研究进入了临床阶段，但总体而言疗效不显著。 1. CXCR3-CXCL9/10/11：IFN-γ是该趋化因子轴的主要驱动因素，联用可以增加效应细胞浸润；瘤内注射CXCL9/10/11等配体或者表达配体的溶瘤病毒，增加效应细胞浸润。 3. CXCR4：使用其拮抗剂 AMD3100， BL-8040可以促进肿瘤的T细胞浸润。 4. CCR4-CCL22/17：用于阻断该轴介导的Treg募集的策略，包括阻断抗体、siRNAs和拮抗剂：（1）CCR4抗体：mogamulizumab (KW-0761)是一种人源化、糖工程IgG1κ单克隆抗体，通过ADCC靶向表达CCR4的细胞。临床试验结果显示它可以消除淋巴瘤中Treg的积累。（2）CCR4小分子抑制剂：FLX475和RPT193，FLX475联合派姆单抗治疗晚期或转移性癌症的1/2期临床试验(NCT03674567)最近已经完成，但尚未被报道；此外GSK 的(GSK2239633) 和AstraZeneca的(AZD-1678，AZD-2098) 也是CCR4的小分子抑制剂。 5. CCL2-CCR2：阻断CCL2-CCR2，可以抑制MDSCs的浸润：（1）抗CCR2抗体：MLN1202，治疗骨转移（NCT01015560）。（2）CCR2小分子抑制剂：PF-04136309，联合白蛋白-紫杉醇/吉西他滨治疗中期静态PDA患者的1b期试验显示，外周血中炎症性单核细胞(IM)减少，而没有在骨髓中积累。但与标准化疗相比，CCR2抑制也会导致肺毒性增加。在另一项1b期试验中PF-04136309和叶酸，不同的标准化疗方案（边缘可切除和局部晚期胰腺癌），是安全的，减少单核细胞从骨髓，TAM浸润原发肿瘤，导致高于预期的客观反应率（49%）。（3）CCR2拮抗剂：CCX872 ，用于治疗胰腺癌，总生存率提高（18个月时29%Vs18.6%）。 6. CCR5：CCR5拮抗剂Maraviroc，在体外模型中将巨噬细胞重新极化为免疫活性表型。目前还在招募的临床试验是卒中后认知障碍：NCT04966429 Safety and Efficacy of Maraviroc in Post-stroke Cognitive Impairment Phase2 7. CXCR1/CXCR2-CXCL8：阻断该轴，抑制肿瘤生长：（1）CXCR1/2抑制剂：Reparixin是一种临床级抑制剂，可在体外抑制乳腺癌的生长。（2）CXCR1/2的小分子拮抗剂：包括SCH479833和SCH527123，在乳腺癌、CRC、自发性结肠癌肝转移和黑色素瘤的异种移植模型中具有抗肿瘤活性。（3）CXCL8阻断抗体：ABX-CXCL8，在异种移植模型中抑制黑色素瘤的生长。总体如麻省总医院Andrew D. Luster教授所言，趋化因子和趋化因子受体很难作为治疗靶点进行开发... Even if chemokines and chemokine receptors represent difficult therapeutic targets, they might help todissect cellular components critical for induction and maintenance of pro- and anti-tumorigenic immune cell states. 参考文献 Hanahan, D. et al. Hallmarks of cancer: the next generation. Cell. 2011; 144: 646-674. Hua, Y. et al. Tumors vs. chronic wounds: an immune cell’sperspective. Front. Immunol. 2019; 10: 2178. Villablanca et al, Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7expression on dendritic cells and dampens antitumor responses. Nat. Med. 2010; 16: 98–105. Binnewies, M. et al, Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity. Cell. 2019; 177: 556–571.e16. Griffith, J.W. et al. Chemokines and chemokinereceptors: positioning cells for host defense and immunity. Annu. Rev. 2014; 32: 659-702. Karan Kohli et al，Key chemokines direct migration of immune cells in solid tumors，Cancer Gene Ther . 2022;29(1):10-21. 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

免疫疗法临床申请

2022-07-18

·佰傲谷BioValley

肿瘤免疫中错综复杂的趋化因子系统

趋化因子系统参与调节细胞迁移、粘附、定位和细胞间相互作用，作用于肿瘤细胞和免疫细胞调节二者细胞活动，高度参与肿瘤的发展过程。根据肿瘤发生过程中所处的阶段、免疫细胞的活化状态、效应与调控反应间的平衡以及趋化因子受体在效应靶细胞和调节性靶细胞上的相对表达，趋化因子会表现出促肿瘤和抗肿瘤两种效应，甚至同一趋化因子作用于不同细胞，具有两种截然相反的效应。一、促瘤效应趋化因子1. CCL2：通过CCL2-CCR2轴募集肿瘤相关免疫抑制细胞；介导肿瘤与肿瘤相关巨噬细胞（TAM）相互作用，提高肿瘤干细胞特性、转移能力和治疗抵抗。2. CXCL1/CXCL8：通过CXCL1/CXCL8-CXCR2轴募集肿瘤相关免疫抑制细胞。3. CXCL12：通过CXCR4-CXCL12轴促进TAM分化为血管周围TAM细胞，提高血管通透性，使肿瘤细胞向血管内浸润；实体瘤增加骨髓基质细胞中CXCL12的表达，导致表达CXCR4的髓样细胞积聚，影响免疫细胞的发育成熟，CXCR4-CXCL12轴参与Treg向骨髓的迁移。4. CCR4：在肿瘤微环境（TME）中募集调节性T细胞（Treg）。5. CCR6：促进Treg细胞在TME原位增殖。6. CCR8：在TME内DC细胞附近募集Treg，并通过抗原识别使Treg具有免疫抑制作用；通过CCR8-CCL1轴增加Foxp3表达维持Treg细胞的免疫抑制能力。7. CCR4+Th2、CCR6+Th17、CXCR3+Th1、CXCR5+Tfh，以上4类趋化因子受体分别在不同细胞中的表达，与Treg抑制功能有一定相关性。二、抗瘤效应趋化因子1. XCL1：通过XCL1-XCR1轴介导cDC1细胞向肿瘤募集，促进cDC1与CD8+T细胞相互作用，促使T细胞扩增和获得效应器功能。2. CXCL11：其表达与髓源性抑制细胞（MDSCs）的丰度和CD8+T细胞浸润程度成反比。3. CCR7：介导cDC1和cDC2细胞从肿瘤向TDLN迁移，启动T细胞的效应功能。4. CCL21：介导T细胞和DC细胞向肿瘤引流淋巴结（TDLN）募集，其表达减少会影响免疫细胞群定位，最终可能导致T细胞活性降低。5. CX3CR1：CD8+T细胞接收到CX3CR1信号才能发挥抗肿瘤作用。三、双效应趋化因子1. CCR5：CCR5-CCL5轴介导cDC1向肿瘤募集，能同时募集Treg细胞和CD8+T细胞；调控TAM表型和功能，介导肿瘤与TAM相互作用，提高肿瘤肝细胞性、转移能力、治疗抵抗2. CXCR3：CXCR3-CXCL9/CXCL10轴也能同时募集Treg和CD8+T细胞；使干细胞样TCF-1+细胞向cDC1细胞募集、在TME中重激活和通过接触IL-2获得效应器功能；调控免疫效应细胞在肿瘤附近的定位。四、药物开发一些趋化因子的研究进入了临床阶段，但总体而言疗效不显著。1. CXCR3-CXCL9/10/11：IFN-γ是该趋化因子轴的主要驱动因素，联用可以增加效应细胞浸润；瘤内注射CXCL9/10/11等配体或者表达配体的溶瘤病毒，增加效应细胞浸润。3. CXCR4：使用其拮抗剂 AMD3100， BL-8040可以促进肿瘤的T细胞浸润。4. CCR4-CCL22/17：用于阻断该轴介导的Treg募集的策略，包括阻断抗体、siRNAs和拮抗剂：（1）CCR4抗体：mogamulizumab (KW-0761)是一种人源化、糖工程IgG1κ单克隆抗体，通过ADCC靶向表达CCR4的细胞。临床试验结果显示它可以消除淋巴瘤中Treg的积累。（2）CCR4小分子抑制剂：FLX475和RPT193，FLX475联合派姆单抗治疗晚期或转移性癌症的1/2期临床试验(NCT03674567)最近已经完成，但尚未被报道；此外GSK 的(GSK2239633) 和AstraZeneca的(AZD-1678，AZD-2098) 也是CCR4的小分子抑制剂。5. CCL2-CCR2：阻断CCL2-CCR2，可以抑制MDSCs的浸润：（1）抗CCR2抗体：MLN1202，治疗骨转移（NCT01015560）。（2）CCR2小分子抑制剂：PF-04136309，联合白蛋白-紫杉醇/吉西他滨治疗中期静态PDA患者的1b期试验显示，外周血中炎症性单核细胞(IM)减少，而没有在骨髓中积累。但与标准化疗相比，CCR2抑制也会导致肺毒性增加。在另一项1b期试验中PF-04136309和叶酸，不同的标准化疗方案（边缘可切除和局部晚期胰腺癌），是安全的，减少单核细胞从骨髓，TAM浸润原发肿瘤，导致高于预期的客观反应率（49%）。（3）CCR2拮抗剂：CCX872 ，用于治疗胰腺癌，总生存率提高（18个月时29%Vs18.6%）。6. CCR5：CCR5拮抗剂Maraviroc，在体外模型中将巨噬细胞重新极化为免疫活性表型。目前还在招募的临床试验是卒中后认知障碍：NCT04966429 Safety and Efficacy of Maraviroc in Post-stroke Cognitive Impairment Phase27. CXCR1/CXCR2-CXCL8：阻断该轴，抑制肿瘤生长：（1）CXCR1/2抑制剂：Reparixin是一种临床级抑制剂，可在体外抑制乳腺癌的生长。（2）CXCR1/2的小分子拮抗剂：包括SCH479833和SCH527123，在乳腺癌、CRC、自发性结肠癌肝转移和黑色素瘤的异种移植模型中具有抗肿瘤活性。（3）CXCL8阻断抗体：ABX-CXCL8，在异种移植模型中抑制黑色素瘤的生长。总体如麻省总医院Andrew D. Luster教授所言，趋化因子和趋化因子受体很难作为治疗靶点进行开发...Even if chemokines and chemokine receptors represent difficult therapeutic targets, they might help todissect cellular components critical for induction and maintenance of pro- and anti-tumorigenic immune cell states.参考文献Hanahan, D. et al. Hallmarks of cancer: the next generation. Cell. 2011; 144: 646-674.Hua, Y. et al. Tumors vs. chronic wounds: an immune cell’sperspective. Front. Immunol. 2019; 10: 2178. Villablanca et al, Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7expression on dendritic cells and dampens antitumor responses. Nat. Med. 2010; 16: 98–105.Binnewies, M. et al, Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity. Cell. 2019; 177: 556–571.e16.Griffith, J.W. et al. Chemokines and chemokinereceptors: positioning cells for host defense and immunity. Annu. Rev. 2014; 32: 659-702.Karan Kohli et al，Key chemokines direct migration of immune cells in solid tumors，Cancer Gene Ther . 2022;29(1):10-21.近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

抗体小分子药物免疫疗法

100 项与 PF-4136309 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性胰腺导管腺癌	临床2期	美国	Pfizer Inc.	2016-05-04
局部晚期胰腺腺癌	临床2期	美国	National Cancer Institute	2012-04-01
慢性丙型肝炎	临床2期	韩国	Pfizer Inc.	2011-01-17
慢性丙型肝炎	临床2期	中国台湾	Pfizer Inc.	2011-01-17
慢性丙型肝炎	临床2期	印度	Pfizer Inc.	2011-01-17
慢性丙型肝炎	临床2期	新加坡	Pfizer Inc.	2011-01-17
慢性丙型肝炎	临床2期	中国香港	Pfizer Inc.	2011-01-17
膝关节炎	临床2期	美国	Pfizer Inc.	2008-08-05
膝关节炎	临床2期	韩国	Pfizer Inc.	2008-08-05

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01226797 (CTgov)	临床2期	慢性丙型肝炎	24	PF-04136309 (PF-04136309)	鏇繭鹹壓膚簾淵艱壓淵(鏇製簾願衊選選簾醖鹽) = 夢齋獵膚觸遞範積夢鏇鬱窪鏇窪淵齋觸壓糧鹽 (淵網膚製鹽積築網壓觸, 製鬱鏇網餘醖獵遞鏇築 ~ 構製製淵顧蓋鏇製繭構) 更多	-	2023-07-27
NCT01226797 (CTgov)	临床2期	慢性丙型肝炎	24	Placebo (Placebo)	鏇繭鹹壓膚簾淵艱壓淵(鏇製簾願衊選選簾醖鹽) = 夢醖顧遞艱壓觸顧鬱顧鬱窪鏇窪淵齋觸壓糧鹽 (淵網膚製鹽積築網壓觸, 壓網遞願製窪鑰醖鹽壓 ~ 壓選廠鏇衊廠艱廠憲顧) 更多	-	2023-07-27
NCT00689273 (CTgov)	临床2期	膝关节炎	159	PF-04136309 (PF-04136309)	醖網鹽積製糧餘製顧糧(壓蓋遞鹽積餘壓蓋襯顧) = 觸網淵繭蓋顧艱願衊鹹遞製願繭窪鑰製廠願醖 (壓壓淵襯醖遞齋蓋觸鹽, 鏇憲構鏇壓構膚構糧膚 ~ 夢淵窪餘願構獵鬱築壓) 更多	-	2021-07-13
NCT00689273 (CTgov)	临床2期	膝关节炎	159	Placebo (Placebo)	醖網鹽積製糧餘製顧糧(壓蓋遞鹽積餘壓蓋襯顧) = 餘鬱遞齋顧艱廠憲窪鹽遞製願繭窪鑰製廠願醖 (壓壓淵襯醖遞齋蓋觸鹽, 齋遞憲鑰蓋願膚齋鹽窪 ~ 鑰獵齋糧鹹顧壓繭簾齋) 更多	-	2021-07-13
NCT02732938 (Pubmed) 人工标引	临床1期	转移性胰腺导管腺癌一线	21	nab-paclitaxel+gemcitabine+PF-04136309	(艱窪餘構繭簾壓憲顧餘) = PF-04136309 500 mg BID 鬱廠醖遞遞製鏇製膚鏇 (積艱鹽壓構廠醖簾獵積 ) 更多	不佳	2020-06-01
NCT02732938 (ESMO2017) 人工标引	临床1期	转移性胰腺腺癌一线	21	nab-paclitaxel+gemcitabine+PF-04136309 (all pts)	(壓繭鬱壓範衊窪鬱鑰網) = Cohort 1, starting dose level: 1 grade 3 drug-related DLT (cognitive disorder), 1 grade 2 and 2 grade 1 rashes. Cohort 2 (1 dose level reduction): 4 (23.5%) grade 3 drug-related DLT (1 scalp dysesthesia, 1 ALT-AST, 1 pneumonia, 1 pneumonitis) 願艱鏇蓋糧製夢夢獵簾 (遞糧醖網製觸積餘膚糧 ) 更多	积极	2017-09-09