Sacituzumab tirumotecan

CHENGDU, China, Nov. 9, 2025 /PRNewswire/ -- From November 6 to 9, the 2025 Chinese Congress on Holistic Integrative Oncology (CCHIO) was held in Kunming, Yunnan. This conference was jointly organized by the Chinese Anti-Cancer Association (CACA), the Tengchong Science Forum Organizing Committee Office, the World Association for Integrative Oncology (WAIO), and the China Institute for Integrative Medicine Development Strategy. Academicians, experts, and scholars from across the nation gathered to focus on innovations in cancer diagnosis and treatment while sharing scientific breakthroughs. At the conference, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company," 6990.HK) presented results from multiple clinical studies on its TROP2 ADC sacituzumab tirumotecan (sac-TMT) as oral presentations. KL264-01/MK-2870-001 On November 7, Professor Sheng Jindong from Tianjin Cancer Hospital presented oral results on the efficacy and safety of sacituzumab tirumotecan (sac-TMT) monotherapy for locally advanced or metastatic endometrial cancer (EC) in a Phase II study at the conference. The endometrial carcinoma (EC) cohort in this study enrolled a total of 158 patients, with 114 patients assigned to the sac-TMT 4 mg/kg group and 44 patients to the sac-TMT 5 mg/kg group. At data cutoff (May 21, 2025), median (range) follow-up was 11.7 months in the 4 mg/kg group and 21.8 months in the 5 mg/kg group. Confirmed objective response rate (ORR) was 30.7% and 34.1% in the 4 mg/kg and 5 mg/kg groups; all responses were partial response (PR). Confirmed and unconfirmed ORR was 35.1% and 36.4% in the 4 mg/kg and 5 mg/kg groups. Median duration of response (DOR) was 9.3 months and 8.7 months in the 4 mg/kg and 5 mg/kg groups. Median progression free survival (PFS) was 6.0 months and 7.3 months in the 4 mg/kg and 5 mg/kg groups. Grade ≥3 treatment-related AEs (TRAEs) occurred in 59 patients (51.8%) and 34 patients (77.3%) in the 4 mg/kg and 5 mg/kg groups respectively; Treatment-related AEs that led to treatment discontinuation was 2 and 1 patient in each group, respectively. In patients with advanced EC, sac-TMT monotherapy showed promising antitumor activity in the ≥2L advanced/metastatic setting and manageable safety. Both the 4 mg/kg and 5 mg/kg groups exhibited manageable safety and tolerability profiles consistent with the known safety characteristics of sac-TMT. These data led to initiation of two ongoing global Phase 3 studies of sac-TMT 4 mg/kg Q2W in advanced EC, which were sponsored and led by MSD. OptiTROP-Lung03 On November 8, Professor Fang Wenfeng from the Cancer Center of Sun Yat-sen University delivered an oral presentation at the conference on preliminary results from a Phase II study evaluating sac-TMT in treating locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations in previously treated patients. As of Dec 01, 2024, 42 patients were enrolled, including 23 patients with EGFR uncommon non-ex20ins mutations and 19 patients with EGFR ex20ins. Patients received sac-TMT 5 mg/kg Q2W until disease progression or unacceptable toxicity. After a median follow-up of 9.9 months, the ORR was 35.7% (15/42, 3 pending confirmation). The disease control rate (DCR) was 85.7%. Responses were durable with the median duration of response (mDoR) not yet reached, and the 6-month DoR rate was 90.9%. The median progression-free survival (mPFS) was 9.5 months (95% CI: 5.6, 10.9). In the subset of patients with uncommon non-ex20ins, the ORR was 34.8% (8/23, 1 pending confirmation); the mPFS was 10.9 months (95% CI: 5.6, NE). In the subset of patients with ex20ins, the ORR was 36.8% (7/19, 2 pending confirmation); the mPFS was 9.0 months (95% CI: 2.4, NE). Grade ≥3 treatment-related adverse events occurred in 52.4% of pts. No TRAE led to treatment discontinuation or death. No cases of interstitial lung disease/pneumonitis were reported. Sac-TMT monotherapy demonstrated promising clinical activity with a manageable safety profile in previously treated advanced NSCLC patients with uncommon EGFR mutations. These findings warrant further investigation of sac-TMT as a potential therapy for this population. OptiTROP-Lung01 Professor Fang Wenfeng also presented results from the non-squamous cohort in the Phase II study evaluating the combination of sac-TMT and tagitanlimab (anti-PD-L1) as first-line therapy for advanced NSCLC during the oral presentation session. As of Dec 30, 2024, 81 patients with non-squamous histology were enrolled. Patients receive sac-TMT (5 mg/kg Q3W or Q2W) plus tagitanlimab (1200 mg Q3W or 900 mg Q2W) until disease progression or unacceptable toxicity. After median follow-up of 17.1 months, the confirmed ORR was 59.3%; The DCR was 91.4%; mDOR was 16.5 months (95% CI: 11.7, 22.1); mPFS was 15.0 months (95% CI: 10.8, 24.8). Among pts with PD-L1 TPS< 1%, the confirmed ORR was 47.1%; mPFS was 12.4 months (95%CI: 7.6, 15.4); while for patients with PD-L1 TPS≥ 1%, the confirmed ORR was 68.1%; mPFS was 17.8 months (95%CI: 14.5, NE). Among patients with PD-L1 TPS≥ 50%, the confirmed ORR was 77.8%; mPFS was 17.8 months (95% CI: 10.8, NE). No TRAE led to treatment discontinuation or death. Sac-TMT in combination with tagitanlimab demonstrated promising antitumor activity in treatment-naive advanced non-squamous NSCLC. The durable clinical activities were observed regardless of PD-L1 expression. This combination therapy showed a tolerable safety profile based on known profiles of the individual agents, with no new safety signals observed. Currently, two Phase 3 registrational studies of sac-TMT, namely (i) sac-TMT in combination with pembrolizumab (KEYTRUDA®1) versus pembrolizumab for first-line treatment of patients with PD-L1 positive locally advanced or metastatic NSCLC, and (ii) sac-TMT in combination with pembrolizumab versus chemotherapy combined with pembrolizumab as first-line treatment for patients with PD-L1 negative locally advanced or metastatic non-squamous NSCLC are in progress. With the goal of addressing patients' urgent clinical needs, Kelun-Biotech has initiated over 30 clinical studies across multiple disease areas including lung cancer, breast cancer, and gynecological tumors. Leveraging its proprietary ADC and novel DC platform, OptiDC™, the Company will continue developing innovative drugs with significant clinical value. This commitment aims to further enhance patient outcomes and contribute corporate strength to advancing the Healthy China initiative. About Sac-TMT Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells. In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macau, and Taiwan). To date, three indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting), EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy and EGFR mutant-positive locally advanced or metastatic non-squamous NSCLC who progressed after treatment with EGFR-TKI therapy. Sac-TMT is the first TROP2 ADC drug approved for marketing in lung cancer globally. In addition, the new indication application for sac-TMT for the treatment of adult patients with unresectable locally advanced, metastatic hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting was accepted by the Center for Drug Evaluation of the NMPA, and was included in the priority review and approval process. As of today, the Company has initiated 9 registrational clinical studies in China. MSD has initiated 15 ongoing Phase Ⅲ global clinical studies of sac-TMT as a monotherapy or with pembrolizumab or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD. About Kelun-Biotech Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 4 projects have been approved for marketing, 1 project is in the NDA stage and more than 10 projects are in the clinical stage. The company has established one of the world's leading proprietary ADC and novel DC platforms, OptiDC™, and has 2 ADC projects approved for marketing, and multiple ADC and novel DC assets in clinical or preclinical research stage. For more information, please visit . References: 1. Pembrolizumab (KEYTRUDA®) is a registered trademark of Merck Sharp & Dohme LLC (MSD), a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. SOURCE Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. 21% more press release views with Request a Demo

While an overall survival win for ivonescimab serves as another validation for the red-hot PD-(L)1xVEGF drug class in the broader cancer landscape, it may not be very competitive in this particular indication. Akeso has data showing ivonescimab can extend the lives of patients with previously treated EGFR-mutated non-small cell lung cancer (NSCLC), results that can give the red-hot PD-(L)1xVEGF bispecific class a boost.The addition of ivonescimab to chemotherapy significantly reduced the risk of death by 26% in patients with EGFR-mutated nonsquamous NSCLC who had tried an EGFR inhibitor, according to the final analysis of the China-only phase 3 HARMONi-A trial. The data were presented Friday at the 2025 Society for Immunotherapy of Cancer annual meeting.With a data cutoff in April 2025 and a median follow-up of 32.5 months, patients who got ivonescimab on top of chemotherapy lived a median 16.8 months, whereas those who received chemo and a placebo lived 14.1 months.The results marked the first time a phase 3 trial of a drug in the hot PD-(L)1xVEGF bispecific class has met the gold-standard overall survival (OS) endpoint.The statistically significant OS showing is an important win for ivonescimab and reads positive for the bispecific class, according to an Oct. 31 preview of the readout from Leerink Partners analysts led by Daina Graybosch, Ph.D.The 26% death risk reduction was an improvement from the 20% posted at a median follow-up of 17.6 months back in December 2023. At that time, with OS data maturity at 52%, the median OS was 17.1 months for the experimental arm and 14.5 months for control.A graphic visualizing the number of deaths shows that starting around 28 months, the roughly 30% remaining patients in the ivonescimab arm experienced relatively stable survival status, with very few new deaths.A flat tail of the OS curve would be “particularly meaningful” because it would suggest an immune mechanism contributed to the bispecific’s clinical benefit, Graybosch’s team said in the note late last month. Because EGFR-mutant NSCLC is relatively insensitive to immunotherapy, the analysts said the regimen being able to mount a benefit here would increase their confidence that the PD-(L)1xVEGF bispecifics can replace anti-PD-1 inhibitors like Merck & Co.’s Keytruda.As the likes of Keytruda have never been able to crack into EGFR NSCLC, ivonescimab’s success shows that its bispecific construct is more than just a simple combination of PD-1 and VEGF inhibition, Akeso CEO Michele Xia, Ph.D., said in an interview with Fierce Pharma. But while the OS win serves as another validation for the closely watched drug class in the broader cancer landscape, ivonescimab may not ultimately win out in this particular indication.A few days ago, China’s Kelun-Biotech unveiled phase 3 data for its Merck-partnered sacituzumab tirumotecan (sac-TMT) showing the TROP2 antibody-drug conjugate lowered the risk of death by 40% versus chemotherapy in Chinese patients with pretreated EGFR-mutant NSCLC. The ADC achieved that result by itself, unlike ivonescimab, which was added to chemo.The median OS was not reached by the time of the interim analysis of the OptiTROP-Lung04 trial, versus the median result of 17.4 months for chemo.In this study, 85.5% of patients in the chemotherapy arm received a subsequent treatment, including 19.6% who got an ADC. For the sac-TMT arm, the numbers were 72.3% and 1.4%, respectively.In HARMONi-A, 62.7% of patients in the ivonescimab arm and 72% in the control group received subsequent therapies. These include 50.3% and 54% on targeted therapies such as another EGFR inhibitor, 5.6% and 5% on an investigational antitumor drug, and 0% and 1.9% on an ADC.However, Xia argued that looking more broadly, PD-1xVEGF and TROP2 ADCs could create treatment synergies rather than competition.The two drug classes approach cancer from two directions. With ivonescimab, Akeso is trying to replace existing PD-1 inhibitors, whereas TROP2 ADCs offer more precise delivery of chemo, Xia noted. That’s why the Akeso CEO suggested that combinations of ivonescimab and ADCs could hold potential in multiple tumor types.Akeso envisions setting ivonescimab as “the choice of combo with all different types of ADCs to work on all different types of tumor indications,” Xia said.The company has an internal ADC platform and will report some initial data next year, she added.A boost for ivonescimab’s profile would be good news for Summit Therapeutics, which holds rights to the drug in the U.S., Europe, Canada and Japan. But as Graybosch noted in her team’s preview, that paradoxically may not entirely be the case here because better outcomes in HARMONi-A would translate into worse performance of the Western subgroup in Summit’s global HARMONi trial.Recently, Summit’s global HARMONi trial, which had a large portion of its participants from the Chinese HARMONi-A trial, failed on its OS endpoint. Because Western patients were enrolled slower than expected, the HARMONi study reached its preplanned OS analysis threshold while data from the Western portion were still immature. The global trial had a similar design in that it measured the performance of ivonescimab and chemo versus chemo and placebo in previously treated EGFR-mutated NSCLC.After a longer follow-up of the Western population, Summit recorded what it called a consistent OS showing between Chinese and Western patients. With a median follow-up of 13.7 months, a 16% death risk reduction was observed for ivonescimab in the U.S. and EU, with median OS of 17 months and 14 months for the two trial arms. That’s compared with a 24% improvement, and 16.7 months and 14 months of median OS, respectively, after a median follow-up of 32.7 months in the Chinese subgroup. The Chinese portion of the HARMONi data appeared to have used the same April 2025 data cutoff as HARMONi-A. The two data sets are slightly different because HARMONi only included about 86% of the HARMONi-A subjects who had tried a third-generation EGFR inhibitor.Despite the similar OS numbers, Graybosch’s team at that time remained skeptical because Summit didn’t provide Western-specific OS curves, arguing that the Western data, which will be critical for an FDA review, were still immature to support Summit’s regional consistency claim.A rough comparison of the OS curves between the two trials appears to show a similar pattern, although the onset of ivonescimab’s advantage seems earlier in HARMONi-A, starting at around five months, compared with HARMONi’s separation occurring after 10 months.As Graybosch pointed out in her Oct. 31 note, it would also be important to understand ivonescimab’s longer-term effects, as well as whether the survival difference between the two treatment arms would narrow among Western patients once they receive powerful subsequent treatments.At least for now, the two trials’ OS curves don’t indicate any negative pullback from the Western population in HARMONi beyond the first few months. But, again, the follow-up time for the Western population was relatively short.  Despite the lack of a statistically significant OS showing as requested by the FDA, Summit has decided to take a risk and file ivonescimab for approval this year.As Jefferies analyst Clara Dong, Ph.D., said in a September note, second-line EGFR-mutated NSCLC represents a relatively small market compared with the broader NSCLC opportunity. Summit has recently tweaked the design of its global HARMONi-3 trial that’s pitting ivonescimab against Keytruda in their respective combinations with chemo in first-line NSCLC. The new design will evaluate patients with nonsquamous and squamous cancers separately rather than lumping them together. “After I saw this long-term final analysis of overall survival of ivonescimab [in HARMONi-A], it really boosted my confidence on the other non-small cell lung cancer results,” Xia said.