ESMO Congress 2026

Sintilimab is a recombinant human IgG4 anti-PD-1 monoclonal antibody ^[3], one of ten approved anti-PD-1 antibodies worldwide ^[1], and its class standing rests on several published registration trials: the ORIENT-16 double-blind phase 3 in 650 patients with unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma comparing sintilimab plus XELOX chemotherapy versus placebo plus chemotherapy for overall survival (including the PD-L1 CPS≥5 subset) ^[3]; the ORIENT-15 double-blind phase 3 in 659 patients with advanced or metastatic oesophageal squamous cell carcinoma in the first line, comparing sintilimab plus cisplatin-based chemotherapy versus placebo plus chemotherapy, with overall survival as the primary endpoint (including CPS≥10 patients) ^[4]; and ORIENT-32, a randomised, open-label phase 2-3 study of sintilimab plus the bevacizumab biosimilar IBI305 versus sorafenib as first-line treatment for unresectable HBV-associated hepatocellular carcinoma ^[2]. A phase 1b study also explored its neoadjuvant use in resectable NSCLC ^[5]. Meanwhile, the low response rate of anti-PD-1/PD-L1 monotherapy and the need for combination strategies were explicitly noted as an unresolved issue in the field ^[1], which forms the backdrop for this study in an anti-PD-1-resistant population.

The update at this meeting is MIZAR-003 (presenter Lu Si): GC101 TIL (IL-2-free, low-intensity lymphodepletion) plus sintilimab versus chemotherapy, a randomised phase 2 study in >=2L anti-PD-1-resistant melanoma (n=101). The key numbers can only be copied verbatim from the on-site posts: mPFS 4.4 vs 1.6 months (another post gives 4.37 vs 1.61 months), HR 0.44; ORR 44% vs 8%; acral subtype 45% vs 8%, mucosal subtype 50% vs 0%, with 73% of the overall population being acral/mucosal; grade >=3 TRAEs 42% vs 31%; 101 patients randomised in ~15 months. Also raised on site was the discussant's question of whether 50% dose sintilimab really changes much.

Relative to prior knowledge, the advance here is this: sintilimab's prior evidence came from solid tumour trials combining it with chemotherapy or anti-angiogenic agents against placebo or sorafenib controls ^[2][3][4], whereas this time it was combined with TIL cell therapy in a melanoma population with limited PD-1 monotherapy response rates ^[1] and resistance to anti-PD-1 therapy, showing randomised, controlled PFS and ORR benefit; meanwhile, the IL-2-free, reduced-intensity lymphodepletion design targets the toxicity problem of TIL therapy, although grade >=3 TRAEs were still 42% vs 31%. The recruitment pace of 101 randomised patients in ~15 months also demonstrates the execution efficiency of this study in China.

The limitations are equally clear: the trial is open-label, chemotherapy is a soft comparator, mPFS remains short in absolute terms (4.4 months), grade >=3 TRAEs reached 42%, and the discussant's question about the contribution of 50% dose sintilimab awaits further data; other endpoints such as OS were not disclosed.