First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial.

However, outcomes remain poor.

然而，治疗结果仍然不佳。

We aimed to evaluate the activity and safety of tiragolumab, an anti-TIGIT monoclonal antibody, plus atezolizumab, an anti-PD-L1 monoclonal antibody, and chemotherapy in treatment-naive locally advanced unresectable or metastatic oesophageal cancer.

我们旨在评估抗TIGIT单克隆抗体tiragolumab联合抗PD-L1单克隆抗体atezolizumab以及化疗在治疗未接受过治疗的局部晚期不可切除或转移性食管癌中的疗效和安全性。

Methods

MORPHEUS-EC is a phase 1b/2, randomised, open-label, umbrella study done at 20 sites in Taiwan, South Korea, Australia, Israel, the UK, and the USA.

MORPHEUS-EC是一项在台湾、韩国、澳大利亚、以色列、英国和美国的20个地点进行的1b/2期、随机、开放标签的伞式研究。

Eligible patients were aged 18 years or older, had treatment-naive, locally advanced unresectable or metastatic oesophageal cancer, and an Eastern Cooperative Oncology Group performance status of 0-1.

符合条件的患者年龄在18岁或以上，患有未经治疗的局部晚期不可切除或转移性食管癌，并且东部肿瘤协作组表现状态为0-1。

Patients were randomly assigned using a permuted-block method to receive tiragolumab (600 mg intravenously every 21 days) plus atezolizumab (1200 mg intravenously every 21 days) and chemotherapy (cisplatin 80 mg/m2 intravenously every 21 days plus intavenous fluorouracil 800 mg/m2 per 24 h on days 1-5 of each 21 day cycle), or atezolizumab and chemotherapy, or chemotherapy alone.

患者使用随机区组方法随机分配接受tiragolumab（每21天静脉注射600毫克）加上atezolizumab（每21天静脉注射1200毫克）和化疗（每21天静脉注射顺铂80 mg/m2，以及每21天周期的第1-5天静脉注射氟尿嘧啶800 mg/m2），或仅接受atezolizumab和化疗，或仅接受化疗。

The primary endpoint was investigator-assessed confirmed objective response rateper Response Evaluation Criteria in Solid Tumours version 1.1 in patients who received at least one dose of each drug for their assigned treatment.

主要终点是由研究者根据实体瘤反应评估标准第1.1版评估的确认客观缓解率，针对接受至少一种指定治疗药物的患者。

This trial is registered with ClinicalTrials.gov, NCT03281369, and is ongoing.

该试验已在ClinicalTrials.gov注册，注册号为NCT03281369，目前仍在进行中。

Results

Between June 5, 2020 and Nov 8, 2022, 152 patients were assigned to the tiragolumab plus atezolizumab and chemotherapy (n=63), atezolizumab and chemotherapy (n=65), or chemotherapy (n=24) groups (136 [89%] were male and 16 [11%] were female, 98 [64%] were Asian and 50 [33%] were White).

2020年6月5日至2022年11月8日期间，152名患者被分配到tiragolumab联合atezolizumab和化疗组(n=63)，atezolizumab和化疗组(n=65)，或仅化疗组(n=24)（136名[89%]为男性，16名[11%]为女性，98名[64%]为亚洲人，50名[33%]为白人）。

Median survival follow-up was 10·9 months (IQR 7·1-17·3) in the tiragolumab plus atezolizumab and chemotherapy group, 11·4 months (IQR 7·9-14·7) in the atezolizumab and chemotherapy group, and 8·7 months (3·9-12·0) in the chemotherapy group.

在tiragolumab联合atezolizumab和化疗组中，中位生存随访期为10.9个月（四分位数间距7.1-17.3），在atezolizumab和化疗组中为11.4个月（四分位数间距7.9-14.7），在仅化疗组中为8.7个月（四分位数间距3.9-12.0）。

Investigator-assessed confirmed objective response ratewas 67·7% (95% CI 54·7-79·1; 42 of 62 patients) in the tiragolumab plus atezolizumab and chemotherapy group, 53·8% (41·0-66·3; 35 of 65) in the atezolizumab and chemotherapy group, and 47·8% (26·8-69·4; 11 of 23 patients) in the chemotherapy group. 49 (79%) of 62, 52 (80%) of 65, and 17 (74%) of 23 patients had a grade 3-4 adverse eventin each group respectively, and 36 (58%) of 62, 33 (51%) of 65, and 11 (48%) of 23 had a serious adverse event.

研究者评估确认的客观缓解率为67.7%（95%置信区间54.7-79.1；62名患者中有42名）在tiragolumab联合atezolizumab和化疗组，53.8%（41.0-66.3；65名患者中有35名）在atezolizumab和化疗组，以及47.8%（26.8-69.4；23名患者中有11名）在化疗组。

The most common treatment-related adverse events were nausea (46 [74%] of 62, 47 [72%] of 65, and 18 [78%] of 23) and decreased appetite (29 [47%], 29 [45%], and 10 [43%]).

最常见的治疗相关不良事件是恶心（62名患者中有46名[74%]，65名患者中有47名[72%]，23名患者中有18名[78%]）和食欲减退（62名患者中有29名[47%]，65名患者中有29名[45%]，23名患者中有10名[43%]）。

No deaths were treatment related.

没有与治疗相关的死亡事件。

interpretation

These results support the additional benefit of tiragolumab combined with atezolizumab and chemotherapy for patients with treatment-naive, locally advanced unresectable or metastatic oesophageal cancer.

这些结果支持了tiragolumab联合atezolizumab和化疗对于未经治疗的局部晚期不可切除或转移性食管癌患者的额外益处。

Further validation of tiragolumab plus atezolizumab and chemotherapy has been performed in the phase 3 SKYSCRAPER-08 trial (NCT04540211).

在第三阶段SKYSCRAPER-08试验（NCT04540211）中，对tiragolumab联合atezolizumab和化疗进行了进一步的验证。

funding

F Hoffmann-La Roche-Genentech.

F Hoffmann-La Roche-Genentech