提携共荣：KEYTRUDA联合LENVIMA的几个数据更新
周末要进行的ASCO和SITC联办的肿瘤免疫学会议上EISAI有几项Pembro联合Lenvatinib的数据披露或者更新，原文在最后，为了便于理解，直接浓缩至表格
之前EISAI也披露一些两药联用的数据，简单的横向对比显示联合疗效好于单药，尤其是大家寄予厚望的uHCC，这里回顾下：
首先看下在NSCLC中的，当时还和pembrolizumab单药治疗NSCLC的KEYNOTE-10的数据简单对比，依旧显示联合优于单药，可以看出更新的结果基本一致——只是DOR和PFS分别修正成NE和7.6mo（5.3-NE）,而且指出high potenial activity in pts who received prior treatment with nivolumab——虽然样本很少，但是还是要提一下；另外至少在这个小样本研究中，临床缓解与PD-L1表达状态无关。期待周末有没有高清无码的图流出
黑色素瘤和尿路上皮癌的数据之前未见有披露，这次应该是首次，但是估计大家也没啥兴趣，就直接看表吧
先前还披露过联合用药在子宫内膜癌EC、RCC、HNC和uHCC的数据，所有的目光应该在uHCC上，这次也没有uHCC的更新
前段时间对EC和RCC又做了更新
摘要
A phase Ib/II trial of lenvatinib plus pembrolizumab innon-small cell lung cancer.
https://meetinglibrary.asco.org/record/170490/abstract
Background:Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3,FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, isan approved monotherapy for previously treated patients (pts) with PD-L1 (+)(tumor proportion score ≥1%) metastatic non-small cell lung cancer (mNSCLC;objective response rate [ORR] 18%). We report interim results of an ongoingphase 1b/2 trial of LEN + PEM in pts with solid tumors, focusing on the mNSCLCcohort.
Methods:In this multicenter, open-label study (NCT02501096), pts withmeasurable, confirmed mNSCLC, ECOG PS ≤1, ≤ 2 prior systemic therapies (phase 2only) received oral LEN (20 mg/day) and PEM (200 mg Q3W, IV). Pts were notpreselected by PD-L1 status. The phase 2 primary end point was ORR at 24 weeks(ORRWK24) by investigator-assessed immune-related RECIST (irRECIST).Secondary end points included ORR, progression-free survival (PFS) and durationof response (DOR).
Results:At data cutoff (March 1, 2018), 21 pts were enrolled: 9 (43%)PD-L1(+), 5 (24%) PD-L1(-), and 7 (33%) not tested. Pts were treatment-naïve(14%); or had 1 (33%), 2 (48%), or ≥3 (5%) prior lines of systemic therapy. ORRWK24was 33.3% (95% CI, 14.6–57.0); other efficacy outcomes aresummarized in the table. Grade 3 and 4 treatment-related adverse events (TRAEs)occurred in 48% and 5% (increased aspartate aminotransferase) of pts. There was1 fatal TRAE (exsanguination; “possibly related” to study treatment). The mostcommon grade 3 TRAEs were hypertension (24%), fatigue (14%), diarrhea (14%),proteinuria (10%), and arthralgia (10%).
Conclusions:LEN + PEM showed promising clinical activity and a manageablesafety profile in previously treated pts with mNSCLC who were not preselectedfor PD-L1 status. Further study is warranted.
Phase Ib/II trial of lenvatinib plus pembrolizumab in advanced melanoma.
https://meetinglibrary.asco.org/record/170492/abstract
Background:
Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3,FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, isapproved for first-line treatment of advanced melanoma (objective responserates [ORR], 21–34%). In preclinical studies, LEN decreased tumor-associatedmacrophage populations, increased CD8+ T cell infiltration, and augmented PD-1inhibitor activity; thus, LEN is a rational combination partner for PEM. Wereport interim results of an ongoing phase 1b/2 trial of LEN + PEM in solidtumors, focusing on advanced melanoma.
Methods:
In this multicenter, open-label study, patients (pts) withmeasurable, confirmed, metastatic melanoma and ECOG PS ≤1received oral LEN (20 mg/day) + PEM (200 mg Q3W, IV). Pts were not preselectedfor PD-L1 status. Tumor assessments were by investigator per immune-relatedRECIST (irRECIST). Phase 2 primary end point was ORR at 24 weeks (ORRWK24).Secondary end points included ORR, progression-free survival (PFS) and durationof response (DOR).
Results:
At data cutoff (March 1, 2018), 21 pts were enrolled: 14(67%) were PD-L1+, 4 (19%) were PD-L1-; 3 (14%) not tested. 38% had ≥1prior anticancer therapy. ORRWK24 was 47.6% (95% CI, 25.7–70.2).All pts had ≥1treatment-related adverse event (TRAE). Grade 3 and 4 TRAEs occurred in 13(62%) and 1 (5%; adrenal insufficiency) pts respectively. There were no fatalTRAEs. Most common any-grade TRAEs were fatigue (52%), decreased appetite(48%), diarrhea (48%), hypertension (48%), dysphonia (43%), and nausea (43%).Dose reduction and interruption due to TRAEs occurred in 13 (62%) and 10 (48%)pts, respectively.
Conclusions:
LEN + PEM was well-tolerated and had encouraging clinicalactivity. The combination may potentially improve on the antitumor activity ofanti-PD-1 monotherapies, supporting further evaluation in advanced melanoma.Clinical trial information: NCT02501096
Phase Ib/II trial of lenvatinib plus pembrolizumab in urothelial cancer.
https://meetinglibrary.asco.org/record/170580/abstract
Background:
Pembrolizumab (PEM), an anti-PD-1 antibody, is approved foradvanced urothelial cancer in the second-line setting (objective response rate[ORR] 21%) and in the first-line setting for patients (pts) ineligible forcisplatin with combined positive score ≥10or ineligible for platinum-based chemotherapy (ORR 29%). Tyrosine kinaseinhibitors such as lenvatinib (LEN; a multikinase inhibitor of VEGFR 1-3, FGFR1-3, PDGFRα, RET and KIT) have demonstrated activity in urothelial cancer andmay reverse the immunosuppressive environment that leads to immuno-oncology(IO) failure. We present a phase 1b/2 trial of LEN + PEM in advanced urothelialcancer.
Methods:
In this multicenter, open-label study, pts with confirmedmetastatic urothelial cancer and ECOG PS of 0 or 1 received oral LEN 20 mg/day+ PEM (200 mg Q3W, IV). Pts were not preselected for PD-L1 status. The phase 2primary end point was investigator-assessed ORR at week 24 (ORRwk24) perimmune-related RECIST (irRECIST). Secondary end points included ORR, durationof response (DOR), and progression-free survival (PFS).
Results:
At data cutoff (March 1, 2018), 20 pts were enrolled: 9(45%) PD-L1(+), 5 (25%) PD-L1(-); 6 (30%) not tested. 4 Pts (20%) weretreatment-naïve; 11 (55%) and 5 (25%) pts had had 1 and 2 lines of prioranticancer therapies, respectively. No pt had received prior IO. ORRwk24 was25% (95% CI: 8.7–49.1). 18(90%) pts had ≥1treatment-related adverse event (TRAE). Grade 3 and 4 TRAEs occurred in 5 (25%)and 5 (25%) pts, respectively. There was 1 fatal TRAE (gastrointestinalhemorrhage). The most common any-grade TRAEs were proteinuria (45%), diarrhea(40%), fatigue (30%), hypertension (30%), and hypothyroidism (30%).
Conclusions:
LEN + PEM demonstrated activity in this study of pts withadvanced urothelial cancer, which included pts receiving later-line treatment,and deserves further investigation. Clinical trial information: NCT02501096