Alphamab Oncology announced the results of two studies of HER2 bispecific antibody KN026 at the European Society of Medical Oncology (ESMO) Annual Meeting, held October 20-24 in Madrid, Spain. KN026-201 is a phase II, open label, multi-center clinical study, evaluating the efficacy, safety, and tolerability of KN026 in combination with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer. Primary results from this study (Poster ID: PD18-08, data as of Aug.

18, 2022) were presented at SABCS 2022, showed promising efficacy and tolerability. The 2-year follow-up results are updated at the 2023 ESMO annual meeting. As of the date of data cut-off, August 4, 2023, 57 subjects were enrolled, the median age was 52 years (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV.

The most common sites of metastasis were lymph nodes, bone, lung, and liver. The confirmed ORR within 55 evaluable subjects was 76.4% (42/55) and DCR was 100% (95% CI 93.51, 100). mDoR follow-up time was 26.3 months (95% CI 23.92, 28.91) and DoR was 26.8m (95% CI 20.73, NE).

The median study follow-up was 29.7m (95%CI: 28.32, 30.59). The mPFS was 26.9 months (95% CI:17.97, NE) and the mOS was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.2% (95% CI: 71.85, 91.45) and 77.9% (95% CI: 64.17, 86.89).

Subjects with no visceral metastases, no brain metastases, or IHC3+ had longer PFS. The incidence of =Grade 3 TEAE was 61.4% (35/57). There were no deaths due to KN026 drug-related AEs in this study.

The incidence of KN026-related Grade=3 TRAE was 40.4% (23/57), including neutrophil count decreased 24.6% (14/57), white blood cell count decreased 12.3% (7/57) and others less than 10%. The incidence of serious adverse events related to KN026 was 10.5% (6/57), including febrile neutropenia 1.8% (1/57), diarrhea 1.8% (1/57), and others. KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC.

After 2 years follow-up, mPFS was 26.9m and the 24-month OS rate was 84.2%, which is very promising. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control group. KN026-208 (NCT04881929) is a phase II, open label, multi-center clinical study, evaluating the efficacy, safety, and tolerability of KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer.

patients were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m2 ivgtt d1, q3w) neoadjuvant treatment. The primary endpoint was total pCR rate (tpCR rate). Secondary endpoints were pCR in the breast (bpCR rate), ORR (objective response rate), safety,PK (pharmacokinetics) and immunogenicity.

Preliminary efficacy and safety results (cut-off date: Sep 10th,2022)were presented at SABCS 2022 (Poster ID: OTC-16-04), showed promising efficacy and safety. The final results are updated at the 2023 ESMO annual meeting. From August 9th, 2021, to July 29th, 2022, a total of 30 patients (pts) were enrolled from 5 sites.

As of Nov. 21st, 2022, the study completed the primary outcome. 28 pts completed the surgery followed by pathological evaluation, and 2 pts discontinued from the study earlier due to AEs.

In FAS, tpCR rate was 56.7% (17/30, 95% CI: 37.43%-74.54%), posterior probability for tpCR>40% was 96.7%; bpCR rate was 60% (18/30, 95% CI:40.60%-77.34%); ORR was 90.0% (27/30, 95% CI: 73.47%-97.89%); confirmed ORR was 86.7% (26/30, 95% CI:69.28%-96.24%). The incidence of CTCAE Grade =3 TEAEs was 53.3% (16/30). The most common (=5%) Grade =3 TEAEs were neutrophil count decreased (50.0%, 15/30), white blood cell count decreased (40.0%, 12/30), and lymphocyte count decreased (10.0%, 3/30).

The incidence of SAE and CTCAE Grade=3 SAE were both 6.7% (2/30). KN026-related SAE occurred in only one patient. No patient had left ventricular ejection fraction (LVEF) declines 10% points or more from baseline accompanied with LVEF<50%; and no patient had LVEF declines 15 % points or more from baseline.