KN026 NDA in Pretreated HER2+ Gastric or GEJ Cancer Accepted by NMPA for Review

The National Medical Products Administration of China has accepted for review the new drug application (NDA) seeking approval of KN026 (anbenitamab injection) plus chemotherapy in patients with HER2-positive, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction (GEJ) cancer who have progressed on at least 1 prior systemic therapy, which must include trastuzumab (Herceptin) plus chemotherapy.1

The application is based on findings from the phase 2/3 KN026-001 trial (NCT05427383). Data from the interim analysis of the phase 3 portion showed that the combination improved progression-free survival (PFS) and overall survival (OS) vs standard of care with no new safety signals. Prior data from the phase 2 portion of the research were shared during the 2024 ESMO Congress and showed that the regimen (n = 35) led to an independent review committee (IRC)–assessed confirmed objective response rate (ORR) of 40.0% (95% CI, 23.9%-57.9%) comprised entirely of partial responses.2 The IRC-assessed disease control rate (DCR) was 80.0% (95% CI, 63.1%-91.6%), the median duration of response (DOR) was 11.7 months (95% CI, 6.0-not reached), the median PFS was 8.6 months (95% CI, 3.8-13.1), and the median OS was 13.2 months (95% CI, 10.6-20.5).

“Currently, there are no approved anti-HER2 therapies for the second-line treatment of HER2-positive gastric cancer,” Alphamab Oncology noted in the news release.1 “KN026 is the first HER2 bispecific antibody to demonstrate positive results in the second-line treatment of gastric cancer in China. Meanwhile, multiple pivotal phase 3 clinical studies of KN026 in gastric cancer and breast cancer are undergoing smoothly, with the aim of benefiting more patients.”

What Did the Phase 2 Portion of the KN026-001 Trial Examine?

The multicenter, open-label, phase 2 study enrolled patients with unresectable or metastatic HER2-positive gastric or GEJ cancer confirmed by histopathological and/or cytological examinations and who previously received at least 1 standard treatment.2 Patients were at least 18 years of age, had at least 1 measurable lesion by RECIST 1.1 criteria at baseline, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and acceptable hematologic, hepatic, and renal function.

They were given KN026 at a dose of 30 mg/kg on day 1 every 3 weeks (Q3W) plus paclitaxel at a dose of 175 mg/m2 on day 1 Q3W or irinotecan at 125 mg/m2 on days 1 and 8 Q3W. Treatment continued until progressive disease, withdrawn consent, a new antitumor therapy was started, patients were lost to follow-up, or death.

The primary end points of the study were safety and IRC-assessed ORR. Secondary end points included investigator-assessed ORR; DCR; DOR; IRC- and investigator-assessed PFS; and OS.

At the time of the data cutoff date of March 26, 2024, a total of 39 patients were enrolled. The median patient age was 59.0 years (range, 34-78). Most patients were male (66.7%), had an ECOG performance status of 1 (84.6%), a primary tumor site of the stomach (71.8%), adenocarcinoma histology (97.4%), and immunohistochemistry 3+ with regard to HER2 status (87.2%). Moreover, 56.4% of patients had 1 to 2 metastatic sites and 43.6% had 3 or more. In terms of prior lines of therapy, 69.2% of patients received 1 prior line, 15.4% received 2 prior lines, and 7.7% received 3 prior lines. Previous therapy included trastuzumab-containing therapy (100%), platinum-containing therapy (92.3%), taxane-containing therapy (46.2%), and immune checkpoint inhibition (30.8%). Lastly, 35.9% of patients had gastrectomy.

What Was Learned About the Safety Profile of KN026 Plus Chemotherapy?

All patients experienced any-grade treatment-emergent adverse effects (TEAEs), with 74.4% of these effects grade 3 or higher. The most common treatment-emergent toxicities experienced by at least 10% of patients included decreased white blood cell count (all grade, 66.7%; grade 3, 28.2%), diarrhea (61.5%; 7.7%), anemia (56.4%; 17.9%), decreased neutrophil count (53.8%; 33.3%), weight loss (41.0%; 2.6%), weakness (41.0%; 10.3%), vomiting (35.9%; 0%), decreased platelet count (30.8%; 2.6%), nausea (25.6%; 2.6%), hypokalemia (25.6%; 5.1%), fever (23.1%; 0%), decreased appetite (23.1%; 0%), alopecia (20.5%; 0%), increased alanine aminotransferase (12.8%; 0%), decreased lymphocyte count (12.8%; 5.1%), chills (10.3%; 0%), hypoesthesia (10.3%; 0%), and epistaxis (10.3%; 0%).

What Else Should Be Known About KN026?

1. In November 2023, the NMPA’s Center for Drug Evaluation granted breakthrough therapy designation to KN026.1 The agent received priority review status in August 2025.
2. Data from a phase 2 study (NCT04881929) shared during the 2023 ESMO Congress indicated that when KN026 was paired with docetaxel, it induced responses with acceptable safety in patients with HER2-positive early or locally advanced breast cancer.3
3. Data from a phase 2 trial (NCT04165993) published in Cancer Communications showed that KN026 plus docetaxel (n = 55) elicited an ORR of 76.4% (95% CI, 63.0%-86.8%) with a median DOR that was not reached in this population.4
4. Data from a phase 2 trial (NCT04521179) published in Clinical Cancer Research showed that when KN026 was combined with KN046 it led to durable responses with manageable toxicity in patients with previously treated HER2-positive breast cancer.5 The ORR was 47.2% (95% CI, 30.4%-64.5%) with a median DOR of 15.2 months (95% CI, 4.1-not evaluable).

References

1. The new drug application for KN026 (anbenitamab injection) has been accepted by the National Medical Products Administration. News release. Alphamab Oncology. September 12, 2025. Accessed September 16, 2025. https://www.alphamabonc.com/en/html/news/2708.html
2. Xu J, Zhao J, Chen Y, et al. Efficacy and safety of KN026 in combination with chemotherapy in patients (pts) with unresectable or metastatic HER2 positive gastric or gastroesophageal cancers (GC/GEJC) after first-line treatment with a trastuzumab-containing regimen. Ann Oncol. 2024;35(suppl 2):S889. doi:10.1016/j.annonc.2024.08.1491
3. Ma L, Yang B, Zhang M, et al. 247P KN026 in combination with docetaxel as neoadjuvant treatment for HER2+ early or locally advanced breast cancer (BC): A single-arm, multicenter, phase II study. Ann Oncol. 2023;34(suppl 2):S282. doi.org/10.1016/j.annonc.2023.09.445
4. Ma J, Wang J, Xu T, et al. Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial. Cancer Commun (Lond). 2025;45(4):476-485. doi:10.1002/cac2.12662
5. Liu J, Song C, Yang Y, et al. Safety and efficacy of KN046 in combination with KN026 in patients with advanced HER2-positive breast cancer: a phase II trial. Clin Cancer Res. 2025;31(12):2379–2385. doi:10.1158/1078-0432.CCR-24-3888.