Sintilimab

The regulatory filing relies on findings from MIZAR-003, a Phase II trial assessing GC101 with sintilimab against chemotherapy. Credit: Asian Isolated / Shutterstock.com. Innovent Biologics has received acceptance from China’s National Medical Products Administration (NMPA) to review its sintilimab and Nolgileucel injection (GC101) combination for advanced melanoma. The submission seeks approval for patients diagnosed with unresectable or metastatic melanoma whose condition has progressed following at least two previous systemic treatments, including anti- programmed death-1 (PD-1) therapy. If cleared, this regimen will mark the 11th approved indication for sintilimab. The regulatory filing relies on findings from MIZAR-003, a randomised, multi-centre, open-label, parallel-controlled Phase II trial assessing GC101 with sintilimab against standard chemotherapy in individuals with prior anti-PD-1 exposure. As of the 12 May 2026 data cut-off date, the study achieved its primary endpoint. Participants receiving the experimental therapy achieved a median progression-free survival of 4.3 months, compared with 1.6 months for those receiving chemotherapy. This demonstrated a 57% reduction in the risk of disease progression or death, reflecting a hazard ratio of 0.43. Adverse events in the study were manageable, with Grade 3 or higher reactions consisting predominantly of haematological toxicities associated with preconditioning. The median duration of adverse events was shorter in the combination cohort at eight days compared with 13 days in the control arm, with most individuals resolving without further therapeutic intervention. Initial data from the trial was presented orally at the ASCO Annual Meeting in June 2026. Innovents oncology chief research and development officer Dr Hui Zhou said: “We are pleased that the 11th indication application for sintilimab has been accepted for review by the NMPA, with the potential to offer a more effective treatment option for patients with advanced melanoma in China. “This acceptance further consolidates the position of sintilimab as a cornerstone therapy in immuno-oncology. It also marks another milestone for us in advancing the full life-cycle management of this product and continuously maximising its clinical value.” Co-developed by Eli Lilly and Company and Innovent, sintilimab, marketed in China as TYVYT, is an immunoglobulin G4 monoclonal antibody directed at PD-1. Its partner therapy, GC101, is a tumour-infiltrating lymphocyte product developed by Juncell Therapeutics via its DeepTIL platform. GC101 does not require high-intensity lymphodepletion or interleukin-2 and is listed in the 2026 CSCO melanoma guidelines, with additional Phase II evaluations underway in non-small cell lung cancer and planned for glioma. Innovent was established in 2011 and has commercialised 20 products to date. The biopharmaceutical developer maintains one application under regulatory review, five candidates across Phase III or pivotal studies, and 20 investigational molecules in early-stage assessment. It also holds more than 30 strategic alliances valued at more than 350bn yuan ($52.4bn) with global partners, including Eli Lilly, Incyte, MD Anderson Cancer Center, Pfizer, Roche, Sanofi, and Takeda. In August, Innovent Biologics and Daiichi Sankyo signed an exclusive agreement to commercialise Vanflyta (quizartinib), an oral type II FLT3 inhibitor, in China.

Sacituzumab tirumotecan, or sac-TMT, has shown a strong tumor progression benefit in first-line, PD-L1-negative non-small cell lung cancer in a China phase 3 trial that could help Merck & Co. close a high-stakes gap in its expansive global development program for the Kelun-Biotech-partnered antibody-drug conjugate. Replacing chemotherapy with sac-TMT alongside Merck’s Keytruda slashed the risk of progression or death by 51% in patients with previously untreated nonsquamous NSCLC with a PD-L1 tumor proportion score of less than 1%. Patients who received Keytruda and sac-TMT went a median 15 months without disease progressing, while the Keytruda-chemo arm lasted 5.7 months. The results are being presented at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid and simultaneously published in The New England Journal of Medicine . While overall survival (OS), a secondary endpoint, was immature with only 20% of patients having passed away, the sac-TMT group showed a strong trend toward an improvement of 42%. The estimated one-year survival rate was 77.6% versus 66.4%, respectively. A 51% progression-free survival (PFS) benefit is “clinically compelling,” Marjorie Green, M.D., Merck’s head of oncology global clinical development, said in an interview with Fierce. With multiple Kelun studies showing similar efficacy strengths, “it just gives me more enthusiasm about the asset and what it’s potentially able to do.” Success of the OptiTROP-Lung06 study has a bigger impact than many other phase 3 studies from China, as it offers clues to a key missing piece in Merck’s plan to shore up its PD-1 leadership in the all-important first-line NSCLC setting by replacing conventional chemo with sac-TMT. With nearly 20 global phase 3 trials underway for sac-TMT, Merck has described the TROP2-directed ADC as a “workhorse” product. But it has yet to move the drug into first-line PD-L1-low or -negative nonsquamous NSCLC, the very setting that crowned Keytruda the PD-1 king. Now, with OptiTROP-Lung06 and an earlier OptiTROP-Lung05 win against Keytruda monotherapy in PD-L1-positive NSCLC, Merck appears ever willing to close that gap. “The Kelun OptiTROP-Lung05 [and] 06 gives us a lot of confidence in the target and to target it across the full spectrum of PD-L1,” Merck’s R&D head Dean Li, M.D., Ph.D., said on the company’s second-quarter earnings call back in August. “Yes, we are going to rethink Keynote-189, which is Keytruda plus chemo, and now we have sac-TMT as an ADC, as a next-gen chemo.” Li suggested that Merck will be “very thoughtful” in choosing the immuno-oncology partner for sac-TMT between Keytruda and its PD-1xVEGF candidate, MK-2010. Earlier this month, the New Jersey pharma launched a global phase 2 solid tumor study pairing sac-TMT with MK-2010. The bar for OptiTROP-Lung06 to impress industry watchers is “pretty high,” Leerink Partners analyst Daina Graybosch, Ph.D., said in an interview with Fierce ahead of ESMO. Gilead Sciences’ rival TROP2 ADC, Trodelvy, recently failed in a phase 3 trial in first-line NSCLC. Trodelvy’s Keytruda combo didn’t significantly improve PFS or OS over Keytruda alone in PD-L1-high patients. In a post-hoc subgroup analysis, the combo showed a bigger treatment effect in East Asia, especially China. Based on Trodelvy’s Evoke-03 data, people would assume a deterioration of efficacy from China to global NSCLC trials for a TROP2 ADC and would therefore need to see a large effect size to buy into OptiTROP-Lung06’s potential in a global population. “I think if [the hazard ratio] is below 0.5, people would be like, ‘whoa, okay,’ that sort of swings some enthusiasm back,” Graybosch said. Now, the trial’s PFS hazard ratio has landed at 0.49, with a 95% confidence interval of 0.36 to 0.65. Before seeing the data, Graybosch said investors would be disappointed if the hazard ratio is worse than 0.65. “Not all ADCs are the same,” Green said in response to a question about Evoke-03, a Merck-sponsored study. “They are so different based upon the linker and the payload and the [drug-to-antibody ratio] that you can get directional information about it. And what I saw was activity of TROP2 ADC in non-small cell lung cancer.” Digging deeper into the OptiTROP-Lung06 data. The study’s chemo arm appeared to have slightly underperformed historical experience. In a subgroup analysis of the global Keynote-189 trial, the median PFS for Keytruda plus chemo reached 6.2 months for PD-L1-negative patients. Separately, in a China-only phase 3 trial, Innovent Biologics’ PD-1 drug Tyvyt and chemo registered a 7.3-month median PFS in PD-L1-negative patients. Nevertheless, the sac-TMT combo’s 15-month median PFS still doubled those historical benchmarks. Green described OptiTROP-Lung06’s control arm performance as “very consistent” with the Keynote-189 data. As to OS, even though the data remained early, the Kaplan-Meier curves documenting patients’ survival status show clear separation between the two arms, and the difference widened with no sign so far of closing back up. Subsequent anticancer treatment appears balanced. Among patients who discontinued study treatment, 57% in the sac-TMT arm and 54.1% in the control group received subsequent treatment. Specifically, 1.9% and 17% of patients received an ADC following disease progression. While the objective response rates were similar, at 50.2% and 47.3% between the experimental and control arms, sac-TMT’s responses were deeper and last longer. Green singled out the ability for people to stay on the sac-TMT regimen and enjoy a long duration of response (DoR) as an important factor for the drug’s overall profile. In the study, sac-TMT doubled the median DoR to 13.6 months. In terms of safety, treatment-related adverse events that resulted in death occurred in one patient (0.4%) for sac-TMT due to respiratory failure, versus 1.3% for control. Grade 3 or above treatment-emergent adverse events happened in 47.6% and 60.6% of patients, respectively. Inflammation of the tissue lining the mouth, or stomatitis, a side effect of interest for sac-TMT, happened in 51.1% of patients receiving the ADC-Keytruda combo, including 2.2% at grade 3. In the chemo-Keytruda arm, the rates were 8.4% and 0%, respectively. Even with the two positive China phase 3 trials and Li’s comment indicating a commitment, Merck still hasn’t yet launched that Keynote-189 successor trial for sac-TMT. Graybosch suspected that the New Jersey pharma is waiting for competitor data from Akeso and Summit Therapeutics’ Harmoni-3 readout for their PD-1xVEGF bispecific ivonescimab in a squamous cohort of first-line NSCLC patients, as well as AstraZeneca and Daiichi Sankyo’s Avanzar trial for their TROP2 ADC Datroway, to better inform its development strategy. “You can imagine what is the potential, and the potential is broad, whether it is something like a sac-TMT/Keytruda combination, or is it something with the [PD-1x]VEGF bispecific,” Green said of Merck’s NSCLC portfolio. “So, lots of work ongoing internally, and I’ll just say stay tuned.”