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427 Efficacy and safety of AK112, an anti-PD-1/VEGF-A bispecific antibody, in patients with platinum-resistant/refractory epithelial ovarian cancer in a Phase 1 study
  1. Jermaine Coward1,
  2. Sophia Frentzas2,
  3. Anna Mislang1,
  4. Bo Gao3,
  5. Charlotte Lemech4,
  6. Xiaoping Jin5,
  7. Baiyong Li5,
  8. Max Wang5,
  9. Kon Yew Kwek5,
  10. Yiting Zhou5 and
  11. Yu Xia5
  1. 1Icon Cancer Centre, South Brisbane, Australia
  2. 2Monash Health, Melbourne, Australia
  3. 3Blacktown Hospital, Blacktown, Australia
  4. 4Scientia Clinical Research, Randwick, Australia
  5. 5Akeso Biopharma Inc, Potomac, USA


Background Platinum-resistant/refractory epithelial ovarian cancer (PROC) is a high unmet medical need with limited treatment options and a median survival of 12–15 months.1 Single agent PD-(L)1 inhibitors have objective response rates (ORR) of less than 10%.2 3 However, combination of nivolumab plus bevacizumab yields a higher ORR of 16.7% in platinum-resistant patients (pts), indicating synergistic activity between PD-1 inhibition and anti-angiogenic therapy in this disease.4 Here, we present initial efficacy and safety data for AK112, a bispecific antibody targeting PD-1 and VEGF-A, in pts with PROC.

Methods Pts with PROC were enrolled in an ongoing Phase 1a/1b study of AK112 (NCT04047290). Tumor assessments based on RECIST v1.1 were performed once every 8 weeks/2 cycles for the first 12 months, and every 12 weeks thereafter.

Results As of 16 July 2021, 19 PROC pts, of which 6 had platinum-refractory disease, have received AK112 at doses ranging from 3 mg/kg to 30 mg/kg Q2W. Seventeen pts (89.5%) had ≥2 lines of prior therapy in the recurrent/metastatic setting and 7 pts (36.8%) had prior bevacizumab. Seventeen pts had at least 1 post-baseline tumor assessment. Median duration of follow-up was 4.5 months. ORR was 29.4% (5/17; 2 clear cell, 3 high-grade serous]). Among the 5 responders, 3 pts received 20mg/kg Q2W AK112 and 1 pt each had 3mg/kg and 10mg/kg Q2W AK112. Median duration of response was not reached. One pt, who had clear cell PROC and received prior immune checkpoint inhibitor (ICI) therapy, had tumor shrinkage of 70% and continued treatment for more than 17 months. Another pt, who had high-grade serous ovarian cancer and prior treatment with bevacizumab, had tumour shrinkage of 65% and continued treatment for more than 4 months. Disease control rate (DCR) was 76.5% (13/17), with tumor shrinkage observed in 11 pts (64.7%). Twelve out of 19 (63.2%) pts experienced treatment-related adverse events (TRAEs). Three pts (15.8%) experienced Grade 3 TRAEs (hypertension and transaminitis in 1 pt; and hypertension and colitis). There were no Grade 4–5 TRAEs. Commonly reported TRAEs were hypertension (15.8%), arthralgia (15.8%), fatigue (15.8%), hypothyroidism (10.5%) and rash (10.5%).

Conclusions The initial results from Study AK112-101 demonstrate that AK112 garners an encouraging anti-tumor activity and a favorable safety profile in patients with platinum-resistant/refractory epithelial ovarian cancer. AK112 will be further evaluated for the treatment of platinum-resistant/refractory epithelial ovarian cancer in a Phase 2 study.

Acknowledgements Akeso Biopharma, Inc would like to thank the patients, investigators and site staff for their participation in this study.

Trial Registration ClinicalTrials.

gov Identifier: NCT04047290


  1. Pujade-Lauraine E, Banerjee S, Pignata S. Management of platinum-resistant, relapsed epithelial ovarian cancer and new drug perspectives. J Clin Oncol 2019; 37:2437–2448.

  2. Disis ML, Taylor MH, Kelly K, et al. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol 2019; 5:393–401.

  3. Matulonis UA, Shapira-Frommer RS, Santin A, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol 2018; 36: suppl abstr 5511.

  4. Liu JF, Herold C, Gray KP, et al. Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. JAMA Oncol 2019;5:1731–1738.

Ethics Approval This study received ethics approval from Bellberry Human Research Ethics Committee (HREC) on 05 Nov 2019 (Application number 2019-05-459-AB). In accordance with ICH Good Clinical Practice Guidelines and the Declaration of Helsinki, study participants gave informed consent voluntarily before participating in this study.

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