China-based Alphamab Oncology (HKG: 9966) updated the clinical studies for its KN046 and KN026 at the San Antonio Breast Cancer Symposium 2022 annual meeting.
KN046/Albumin Paclitaxel in Metastatic TNBC
The Phase II clinical trial is designed to evaluate the efficacy, safety, and tolerability of KN046 combined with albumin paclitaxel in the treatment of metastatic triple-negative breast cancer (TNBC). The subjects received albumin paclitaxel combined with different doses of KN046. Cohort A included 16 patients, receiving KN046 at 3mg/kg Q2W; Cohort B included 11 patients who received KN046 at 5mg/kg Q2W.
The median follow-up time was 27.93 months. The ORR of 25 patients with assessable efficacy was 44.0%, and the DoR was 11.9 months; the DCR was 96.0%. The median PFS was 7.33 months. The median OS is not yet mature, however, the preliminary result is 27.73 months, and the 2-year OS rate is 60.1%. The combo showed OS benefits in both PD-L1 positive and negative patients, and was well tolerated. No treatment-related deaths occurred.
KN026/Docetaxel in First-Line HER2 Positive Breast Cancer
The Phase II clinical study is designed to assess the efficacy and safety of KN026 combined with docetaxel for the treatment of HER2-positive recurrent/metastatic breast cancer without first-line systematic treatment. The study enrolled 57 patients who were treated with 30 mg/kg Q3W KN026 combined with 75 mg/m2 Q3W docetaxel.
The median follow-up time was 16.6 months. The ORR and DoR of 55 patients with assessable efficacy were 76.4% and 24.0 months respectively; the DCR was 100%. The median PFS was 25.4 months. The median OS has not been reached, and the OS rates of 12 months, 18 months, and 24 months were 93.0%, 91.2%, and 91.2% respectively. KN026 combined with docetaxel produced a significant effect and long-term survival benefit. The safety was good, and KN026 drug-related adverse events caused no deaths.
KN026/Docetaxel as a Neoadjuvant Treatment of HER2-Positive Early or Locally Advanced Breast Cancer
The single-arm, multicenter, phase II study is designed to evaluate the efficacy and safety of KN026 combined with docetaxel as a neoadjuvant treatment of HER2-positive early or locally advanced breast cancer. The study enrolled 30 patients who received 4 cycles of new adjuvant treatment with KN026 (30mg/kg, Q3W) and docetaxel (75mg/m2, Q3W).
Among the 20 patients who completed a surgical and pathological evaluation, the tpCR rate was 50%, the bpCR rate was 55%, and the ORR was 100%. The incidence of grade 3 and above SAEs was 6.7%, and the incidence of KN026-related SAEs was 3.3%. No patient had severe cardiac toxicity. Therefore, the combo as a neoadjuvant treatment of HER2-positive early or locally advanced breast cancer patients is promising, with significant clinical efficacy and controllable safety.
KN046 and KN026: Mechanisms and Clinical Trials
KN046, a bispecific antibody (BsAb) targeting both programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is subject to close to 20 clinical studies in non-small cell lung cancer, triple-negative breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, thymic carcinoma, and others, with good safety and efficacy results.
KN026, a potential next-generation HER2-targeted therapy that simultaneously combines two HER2 epitopes to enhance the killing effect on tumor cells, has obtained an umbrella IND approval in China and IND approval in the US. The drug, subject to multiple Phase I/II clinical studies concurrently in China and the US, has shown good preliminary efficacy in advanced HER2+ breast cancer and gastric or gastroesophageal junction cancer. The drug is also undergoing a pivotal clinical study combined with chemotherapy in HER2-positive gastric cancer that has failed first-line treatment.-Fineline Info & Tech
