Neoadjuvant PD-1 and LAG-3-targeting bispecific antibody and other immune checkpoint inhibitor combinations in resectable melanoma: the randomized phase 1b/2 Morpheus-Melanoma trial.

The NADINA trial evaluating neoadjuvant nivolumab plus ipilimumab and the SWOG-1801 trial evaluating neoadjuvant pembrolizumab have demonstrated superior clinical outcomes with neoadjuvant versus adjuvant checkpoint inhibition.

NADINA试验评估了新辅助纳武单抗联合伊匹木单抗，而SWOG-1801试验评估了新辅助派姆单抗，这两项试验均显示新辅助与辅助检查点抑制治疗相比，临床结果更优。

Morpheus-Melanoma was a phase 1b/2, randomized umbrella trial evaluating tobemstomig (anti-PD-1/anti-LAG-3 bispecific antibody; n = 40), tobemstomig plus tiragolumab (anti-TIGIT monoclonal antibody; n = 20) and atezolizumab (PD-L1-targeting monoclonal antibody) plus tiragolumab (n = 20) versus nivolumab (anti-PD-1 monoclonal antibody) plus ipilimumab (anti-CTLA-4 monoclonal antibody; n = 22) in stage III melanoma.

Morpheus-Melanoma 是一项 1b/2 期、随机的伞式试验，评估了 tobermstomig（抗 PD-1/抗 LAG-3 双特异性抗体；n = 40）、tobemstomig 加 tiragolumab（抗 TIGIT 单克隆抗体；n = 20）以及 atezolizumab（靶向 PD-L1 的单克隆抗体）加 tiragolumab（n = 20）与 nivolumab（抗 PD-1 单克隆抗体）加 ipilimumab（抗 CTLA-4 单克隆抗体；n = 22）在 III 期黑色素瘤中的效果。

The primary endpoint was pathological response by independent pathological review.

主要终点是独立病理审查的病理反应。

Additional endpoints included safety and exploratory biomarkers.

次要终点包括安全性评估和探索性生物标志物。

Here tobemstomig showed a similar pathological response rate (pRR) versus nivolumab plus ipilimumab (80.0% (32/40) versus 77.3% (17/22)); major pathological responses were less frequent with tobemstomig versus nivolumab plus ipilimumab treatment (62.5% (25/40) versus 72.7% (16/22)).

在此研究中，tobemstomig显示出与nivolumab联合ipilimumab相似的病理反应率（pRR）（80.0%（32/40）对比77.3%（17/22））；然而，与nivolumab联合ipilimumab治疗相比，tobemstomig的主要病理反应较少（62.5%（25/40）对比72.7%（16/22））。

Tobemstomig plus tiragolumab and atezolizumab plus tiragolumab showed a lower pRR versus nivolumab plus ipilimumab (60.0% (12/20) and 45.0% (9/20) versus 77.3% (17/22), respectively).

Tobemstomig联合tiragolumab和atezolizumab联合tiragolumab与nivolumab联合ipilimumab相比，显示出较低的pRR (分别为60.0% (12/20)和45.0% (9/20)对比77.3% (17/22))。

Tobemstomig demonstrated improved safety versus nivolumab plus ipilimumab, with 2.5% (1/40) and 22.7% (5/22) of patients experiencing grade 3 or higher treatment-related adverse events (TRAEs), respectively, and 0% (0/40) and 13.6% (3/22) of patients discontinuing treatment due to TRAEs, respectively.

Tobemstomig显示出比nivolumab联合ipilimumab更好的安全性，分别有2.5% (1/40)和22.7% (5/22)的患者经历了3级或更高级别的治疗相关不良事件(TRAEs)，以及分别有0% (0/40)和13.6% (3/22)的患者因TRAEs而停药。

Grade 3 or higher TRAEs were reported by 15% (3/20) of patients in the tobemstomig plus tiragolumab arm and by no patients in the atezolizumab plus tiragolumab arm.

在托贝莫司汀加替拉利单抗组中，有15%（3/20）的患者报告了3级或更高级别的治疗相关不良事件（TRAEs），而在阿替利珠单抗加替拉利单抗组中没有患者报告此类不良事件。

Baseline CD8+ and CD3+ tumor-infiltrating T cell density, IFNγ pathway and effector T cell gene expression, tumor mutational burden and pre-surgery circulating tumor DNA correlated with pathological response across treatments.

基线时的CD8+和CD3+肿瘤浸润T细胞密度、IFNγ通路和效应T细胞基因表达、肿瘤突变负荷以及术前循环肿瘤DNA与各治疗组的病理反应相关。

In conclusion, in the Morpheus-Melanoma study, tobemstomig demonstrated a similar pathological response and improved safety profile versus nivolumab plus ipilimumab in patients with resectable stage III melanoma.

总之，在Morpheus-Melanoma研究中，tobemstomig在可切除的III期黑色素瘤患者中显示出与nivolumab联合ipilimumab相似的病理反应，并改善了安全性。

ClinicalTrials.gov identifier: NCT05116202 .

ClinicalTrials.gov注册号：NCT05116202。