KN026 Combo Boosts PFS in Pretreated HER2+ Gastric/GEJ Cancer

Complete efficacy and safety results from the KN026-001 trial are anticipated to be shared at an upcoming international academic meeting.

Adding the anti-HER2 bispecific antibody KN026 to chemotherapy led to a clinically and statistically significant meaningful improvement in progression-free survival (PFS) vs placebo plus chemotherapy among patients with HER2-positive, advanced, unresectable, or metastatic gastric or gastroesophageal junction (GEJ) cancer who had received at least one previous line of therapy, based on interim findings from the phase 2/3 KN026-001 trial (NCT05427383).¹

Along with PFS data reported by the trial’s independent data monitoring committee at the first interim analysis, KN026 plus chemotherapy also displayed early signals of an overall survival (OS) advantage vs the placebo regimen.

Full efficacy and safety data from the KN026-001 trial are expected to be presented at an upcoming international academic conference.

KN026 is a novel anti-HER2 bispecific antibody designed to bind two distinct epitopes of the HER2 receptor. In this pivotal trial, it was evaluated in combination with chemotherapy in the second-line or later setting for patients with HER2-positive advanced gastric or GEJ cancer.

The Center for Drug Evaluation of the National Medical Products Administration (NMPA) in China has granted breakthrough therapy designation to KN026 in combination with chemotherapy for the treatment of patients with HER2-positive gastric or GEJ cancer whose disease progressed following standard first-line therapy.

KN026-001 Trial Design

The randomized, multicenter, phase 2/3 study enrolled patients at least 18 years of age with histologically or cytologically locally advanced, recurrent, or metastatic gastric or GEJ that was HER2 positive (immunohistochemistry [IHC] 3+; or IHC 2+/in situ hybridization+).² Disease progression of first-line therapy with trastuzumab (Herceptin) plus chemotherapy was required. If patients received a trastuzumab-containing regimen in the neoadjuvant or adjuvant setting, that was considered first-line therapy if patients experienced disease progression during treatment or within 6 months of finishing treatment.

In the first stage of the study, patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria; those enrolled in stage 2 needed at least 1 evaluable lesion at baseline per RECIST 1.1 criteria. An ECOG performance status of 0 or 1, and a life expectancy of at least 3 months were also required for all patients.

Stage 1 of the study was open label and nonrandomized, and all patients received KNO26 plus chemotherapy.

In stage 2, patients were randomly assigned to received intravenous KN026 at 30 mg/kg or placebo on day 1 of each 21-day cycle. Chemotherapy options for patients in both arms included paclitaxel at 175 mg/m² on day 1 of each cycle; docetaxel at 75 mg/m² on day 1; or Irinotecan at 125 mg/m² on days 1 and 8.

The co-primary end points of the phase 3 portion of the trial are PFS and OS, both assessed by an Independent Review Committee (IRC). Secondary end points included overall response rate (ORR), disease control rate, duration of response (DOR), investigator-assessed PFS, and safety.

KN026’s Efficacy Beyond the GI Setting

Findings from a phase 2 trial (NCT04165993) published in Cancer Communications showed that efficacy-evaluable patients with previously untreated, HER2-positive locally advanced or metastatic breast cancer (n = 55) treated with KNO26 plus docetaxel achieved an ORR of 76.4% (95% CI, 63.0%-86.8%), including 3 complete responses and 39 partial responses.³ The median DOR was not yet reached (NR; 95% CI, 20.7 -NR). The 12-, 24-, and 30-month DOR rates were 85.2%, 59.3%, and 51.6%, respectively. Furthermore, the clinical benefit rate (CBR) was 85.5% (95% CI, 73.3%-93.5%).

References

1. A pivotal phase II/III clinical study of anti-HER2 bispecific antibody KN026 has met the primary endpoint of PFS at interim analysis. News Release. May 1, 2025. Accessed May 1, 2025. https://www.alphamabonc.com/en/html/news/2669.html
2. KN026 in combination with chemotherapy in HER2 positive gastric cancer subjects who have failed first-line therapy. ClinicalTrials.gov. Updated December 19, 2023. Accessed May 1, 2025. https://clinicaltrials.gov/study/NCT05427383
3. 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). Published online January 18, 2025. doi:10.1002/cac2.12662