HONG KONG, Jun 6, 2022 -- Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, released clinical details in poster discussion featuring a phase II study from Ivonescimab (PD-1/VEGF BsAbs, AK112) in combination with chemotherapy for advanced non-small cell lung cancer (NSCLC) at 2022 ASCO Annual Meeting.
AK112 in combination with chemotherapy demonstrated a favorable safety profile and better efficacy results compared to PD-1/PD-L1 antibody combined with chemotherapy +/- anti-angiogenic agents combination therapy in patients with advanced NSCLC.
Summary of the clinical results:
- AK112 in combination with chemotherapy for advanced NSCLC showed favourable safety profile
- No significant difference in the incidences of TRAEs between the squamous and the non-squamous NSCLC patients (30.1% of enrolled patients had squamous NSCLC (SQ-NSCLC), of which 52% were central type SQ-NSCLC).
- No serious anti-VEGF-related toxicities such as bleeding and perforation.
- AK112 in combination with chemotherapy showed better anti-tumor activity in advanced NSCLC patients in various sub-types compared to PD-1/PD-L1 antibody combined with chemotherapy +/- anti-angiogenic agents combination therapy
In cohort 1(previously untreated advanced NSCLC patients without EGFR/ALK alterations), efficacy results were encouraging with a more prominent efficacy advantage in squamous NSCLC patients:
- Among all patients, median progression-free survival (PFS) was not reached, and 6-month PFS rate was 78.8%.
- In patients with SQ-NSCLC, median follow-up time was 7.9 months, objective response rate (ORR) was 77.8%, disease control rate (DCR) was 100%, and 6-month PFS rate was 83.3%, which are encouraging compared to approved PD-1 combined with chemotherapy therapies.
In cohort 2 (advanced NSCLC patients who failed to prior EGFR-TKI therapy):
- ORR and DCR were 68.4% and 94.7% respectively.
- Median PFS was 8.2 months, 6-month PFS rate was 69.3%.
In cohort 3 (advanced NSCLC patients who failed in prior platinum-based doublet chemo with anti-PD-1/PD-L1 therapy):
- ORR was 40.0%, DCR was 80%.
- Median PFS was 6.6 months, 6-month PFS rate was 51.1%.
As of March 20, 2022, in this multi-cohort, multi-center phase II study, a total of 83 patients with advanced NSCLC had been treated with AK112 in combination with chemotherapy for up to 12 months and an average dosing time of 7.56 months.
Akeso is conducting a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy (NCT05184712). A phase III head-to-head study of AK112 monotherapy versus Pembrolizumab monotherapy in the first-line treatment of NSCLC is also ongoing.
There are currently no immunotherapy regimens approved globally for patients with EGFR-mutated NSCLC who failed to prior EGFR-TKI therapy. According to the ORIENT-31 study released at the ESMO Congress 2021, Sintilimab with IBI305 (Bevacizumab biosimilar) plus platinum-based doublet chemotherapy had an ORR of 43.9% and a median PFS of 6.9 months in patients with EGFR mutated non-squamous NSCLC who progressed after EGFR-TKI therapy.
There are currently no immunotherapy regimens approved for NSCLC patients who failed in prior platinum-based doublet chemo with anti-PD-1 therapy. According to the MRTX-500 study released at the ESMO Congress 2021, Nivolumab plus Sitravatinib had an ORR of 18%, a DCR of 75%，a median PFS of 5.7 months and a 6-month PFS rate of 45% in patients with NSQ-NSCLC progressing on or after prior checkpoint inhibitor (CPI) therapy. According to the CANOPY-2 study released at the ESMO Congress 2021, docetaxel had an ORR of 14%, median PFS of 4.2 months, and 6-month PFS rate of 34% in advanced or metastatic NSCLC patients.
 Lu S, Wu L, Jian H, et al. VP9-2021: ORIENT-31: Phase III study of sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy. Ann Oncol. 2021 Nov 19, DOI: https://doi.org/10.1016/j.annonc.2021.10.007.
 Ticiana A. Leal et al. MRTX-500: Phase 2 Trial of Sitravatinib + Nivolumab in Patients With Nonsquamous Non–Small-Cell Lung Cancer Progressing on or After Prior Checkpoint Inhibitor Therapy. 2021 ESMO. Abstract # 1190O.
 Luis Paz-Ares,et al. Canakinumab + docetaxel for the second- or third-line treatment of advanced NSCLC: CANOPY-2 Phase III results. 2021 ESMO. Abstract # 1194MO.
 Disclaimer: the study mentioned above is for reference only. It doesn't necessarily represent the latest clinical study ongoing for the same indication, and it is not a head-to-head study derived from AK112 clinical trial.