Ivonescimab

iStock, piyaphat50 Treatment with the TROP2 ADC sac-TMT led to a 70% objective response rate and progression-free survival was “significantly improved” as compared to placebo—the second positive readout for the asset this week. Merck’s Chinese partner Kelun-Biotech appears to have validated the use of a TROP2 ADC along with immunotherapy—specifically the best-seller Keytruda—in first line lung cancer, potentially setting a new treatment paradigm, analysts said. But this indication will be tough to crack with plenty of competition looming, wrote Leerink Partners in a Friday morning note to investors. Kelun revealed data from the Phase 3 OptiTROP-Lung05 study of sacituzumab tirumotecan (sac-TMT) in an abstract posted Friday ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, which will kick off on May 29 in Chicago. The ADC was tested in 413 Chinese patients who had previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) with certain gene mutations. Sac-TMT was added to a regimen with Keytruda while the placebo group received the immunotherapy alone. Treatment with sac-TMT led to a 70% objective response rate (ORR) and progression-free survival (PFS) was “significantly improved” as compared to placebo. Median PFS was not yet reached at the cutoff point of 10.5 months, while the group that received immunotherapy alone had a PFS of 5.7 months. Overall survival (OS) was immature but Kelun said the trend was positive. This is the second positive readout for sac-TMT this week heading into ASCO, with Merck announcing on May 18 that the ADC demonstrated significantly better OS and PFS in patients with late-stage endometrial cancer. Cancer Merck’s billion-dollar Kelun bet pays off as TROP2 improves survival in endometrial cancer Merck and Kelun-Biotech’s antibody-drug conjugate significantly improved progression-free and overall survival in a pivotal endometrial cancer study, though the companies have yet to specify when they plan to approval. May 19, 2026 · 2 min read · Tristan Manalac Read more Leerink was particularly impressed by the ORR rate in NSCLC, which “compares favorably” to chemo plus Keytruda. That combo achieved about 56%–58% in this population. PFS was also strong in a subgroup of patients with high PD-L1 expression, which the firm said “confirms the superiority of the doublet over global standard-of-care” Keytruda. The study also showed “impressive safety and low discontinuation rates,” according to Leerink. Kelun reported that treatment-emergent adverse events grade 3 or under—severe but not immediately life-threatening side effects—occurred in more than half of patients who received sac-TMT. That’s compared to 31% of patients in the Keytruda-only group. Plenty of competition Leerink said the results “appear supportive of the broader TROP2 ADC + IO strategy in [first line] NSCLC . . . but this is a high bar.” More details on the study will be showcased at the ASCO meeting—the largest gathering of oncologists in the U.S. Leerink said the discussion will get into the weeds on the true potential of the ADC-Keytruda combo. But still, the results are a positive for Merck, according to the analyst. “For us, details in the abstract are sufficient to drive MRK upside of +5%, given sac-TMT is one of few internal programs broad enough to drive more certain growth through the Keytruda [loss of exclusivity] period and investors have been relatively lackluster about the program,” Leerink wrote. Earnings Merck drops early-stage TROP ADC, keeps deal doors open as Keytruda clock ticks On the heels of several big buys, Merck still has eyes for M&A—particularly in the oncology, immunology and cardiometabolic spaces—as the quest continues for a candidate that can top Keytruda. April 30, 2026 · 5 min read · Gabrielle Masson Read more The data release also had Leerink comparing other companies’ programs with readthrough to the ADC-immunotherapy clinical win. AstraZeneca’s Dato-DXd, for example, had a 55% ORR rate when added to Keytruda in the Phase 1b TROPION-Lung02 study—well short of the 70% rate put up by Kelun. The Daiichi Sankyo-partnered program also had higher discontinuation rates. Leerink also considered Akeso’s ivonescimab, a China-developed asset that Summit Therapeutics is testing for the U.S. market. Ivonescimab is a VEGF-A/PD-(L)1 bispecific, rather than an ADC, but could compete with sac-TMT in the same lung indication. Leerink said the OptiTROP-Lung05 data is “neutral” for Akeso’s program, despite having higher PFS, ORR and overall survival as compared to the Phase 3 HARMONi-2 trial. Merck is also developing a VEGF-A/PD-1 therapy called MK-2010, which could be paired with sac-TMT in a double or triple combination for first line lung cancer. The U.S. pharma paired up with Kelun , a subsidiary of China-based Sichuan Kelun Pharmaceutical, in December 2022 with a massive licensing deal worth up to $9.3 billion. Merck nabbed seven ADC programs, with Kelun retaining rights to their development in China. Besides lung and endometrial cancer, sac-TMT previously showed a survival benefit in gastric cancer. .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });

Much of the attention heading into the annual ASCO meeting next week has focused on Summit Therapeutics and Akeso’s plenary presentation for their bispecific drug ivonescimab. But two of ivonescimab’s biggest competitors are also releasing new data in Chicago: pumitamig, from BioNTech and Bristol Myers Squibb; and PF’4404, from the partnership between Pfizer and 3SBio. Initial disclosures came Thursday afternoon with the release of conference abstracts, showing early results roughly on par with ivonescimab in first-line lung cancer. After a few years of hype over ivonescimab — thanks to some elite gamesmanship from Summit executives — the rest of the drug class is finally trickling out data from both global and China-only studies. Taken together, the research is likely to paint a clearer picture of how these experimental therapies, which target PD-1 and VEGF, will ultimately help patients in different cancer settings. Ivonescimab remains the field’s leader: The FDA is currently reviewing the drug in a specific form of lung cancer, with a decision expected by November. But opportunity remains for others to compete. BioNTech and Bristol Myers have lined up a slate of at least seven pivotal trials to read out over the next few years, and the companies are planning to focus on combinations with BioNTech’s cancer pipeline. Meanwhile, Pfizer is aiming to pair PF’4404 with some of the drugs it acquired from Seagen. And there will be more data to come next weekend. Trial investigators will expand upon the data included in Thursday’s abstracts during oral presentations in Chicago. Pumitamig’s data come from the Phase 2 portion of a global Phase 2/3 study called ROSETTA Lung-02. Researchers enrolled patients with both non-squamous and squamous non-small cell lung cancer as a first-time treatment. The drug was given in combination with chemotherapy, with the type of chemo regimen differing based on whether patients had non-squamous or squamous tumors. There were 23 patients in the non-squamous cohort, 21 of whom could be evaluated for efficacy; and 21 in the squamous group, 19 of whom could be measured for efficacy. In the non-squamous cohort, 14 of 21 patients saw their tumors shrink by at least 30% with pumitamig plus chemo across two dose levels, equaling a 66.7% objective response rate (ORR). Among the 19 evaluable patients with squamous tumors, 14 saw tumor shrinkage surpass 30% across the dosing levels of the drug-chemo combination, for an ORR of 73.7%. The median duration of treatment was short — only 4.5 months so far. Though early, those figures are about the same rates of response that ivonescimab produced when it was going through its own Phase 2 study (the usual cross-trial caveats apply). At ASCO 2023, Akeso presented data from a China-only study showing a 55% ORR in 72 non-squamous patients, and a 75% ORR in 63 squamous patients. Follow-up was a lot longer in the Akeso study at that point — median duration of response was 15.4 months in the non-squamous group and not reached in the squamous cohort. But both trials enrolled patients in the same treatment setting. Akeso’s trial was also run only in China, whereas ROSETTA Lung-02 is enrolling individuals across four continents. The Phase 2 part of BioNTech and BMS’ study is designed to pick which dose the companies want to move into Phase 3. The lower dose appears to be the early frontrunner, as eight of 11 non-squamous (72.7%) and nine of 11 squamous (81.8%) patients responded. For Phase 3, pumitamig’s efficacy will be measured in a trial designed similarly to Summit’s HARMONi-3 study, which is also looking at a global population and comparing the drug-chemo combo to Merck’s Keytruda plus chemo. Both studies are also separating patients by non-squamous and squamous tumor types. Earlier this month, Summit’s stock price dipped in a sign of investor frustration at a HARMONi-3 update that said its independent data monitoring committee recommended the study “continue as planned,” rather than stop it early for efficacy. Most took that to mean ivonescimab was not able to meet statistical significance in an interim analysis of progression-free survival, though Summit has not explicitly spelled that out. PF’4404’s data, meanwhile, come from a China-only Phase 2 study run by 3SBio. Researchers looked at whether first-line NSCLC patients could respond to PF’4404 as a monotherapy — none received chemo. These data are also more mature than those for pumitamig, with a median follow-up time of 15.2 months. Among 34 patients who received the “FDA-aligned dose” of PF’4404 as of Nov. 28, 2025, 23 saw their tumors shrink by at least 30%, good for a 67.6% ORR. The median progression-free survival was 12.4 months, while the median overall survival was not reached. Researchers also broke down the data by non-squamous and squamous tumors as well. In the non-squamous group, 14 of 22 patients saw at least 30% tumor shrinkage with a median PFS of 12.4 months. Median duration of response and OS were not reached. For the squamous cohort, nine of 12 patients achieved 30% tumor shrinkage. These patients had a median duration of response of 6.2 months and a median PFS of 8.9 months. Median OS was not reached. The results represent a slight improvement over data 3SBio presented at ASCO last year, as two additional patients reached the 30% tumor shrinkage threshold. Last year, 3SBio had reported only 21 of 34 patients responded to the drug at this dose level. Trying to compare these PF’4404 data to ivonescimab’s early results is more challenging. In 2022, Akeso did present monotherapy data from a Phase 1b/2 China-only study, showing a 37.9% ORR at the dose it moved forward into larger studies. But Akeso had the disadvantage of going first in this drug class and was still figuring out where it might work best. Trial investigators also allowed second-line patients to enroll in that Akeso study. A more apt comparison for PF’4404 might be Summit and Akeso’s HARMONi-2 study, though it was a Phase 3. That trial, while much larger than 3SBio’s Phase 2, looked at ivonescimab monotherapy compared to Keytruda alone and read out to much fanfare in 2024. Median PFS was 11.1 months, compared to 5.8 months for Keytruda, in first-line Chinese patients.