Coherus BioSciences, Inc. announced data from the lead-in portion of the Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (uHCC). These data are being presented at the 2024 ASCO Gastrointestinal Cancers Symposium taking place January 18-20, 2024 at Moscone West in San Francisco, California. Interleukin (IL)-27 is an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment.

Casdozo is a first-in-class antibody, and the only clinical stage immunomodulatory cytokine antagonist targeting IL-27. Lead-in portion of Phase 2 clinical trial design: The open-label lead-in portion of the Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 patients with treatment-naïve uHCC. Patients received casdozo 10 mg/kg IV q3w, in combination with atezo (1,200 mg) and bev (15 mg/kg).

The primary endpoint of the lead-in portion of the study was safety and tolerability. Key secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). Further [Phase 2] clinical development of cazdozo in HCC is planned to evaluate casdozo/toripalimab (anti-PD-1 antibody)/bev.

Lead-in portion of Phase 2 clinical trial data As of the data cutoff date (November 9, 2023): Triplet blockade of the IL-27, PD-(L)1 and VEGF pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in IO naïve HCC. Triplet combination treatment was well tolerated with side effect profile consistent with known adverse event (AE) profiles of atezo/bev. Encouraging early activity with casdozo/atezo/bev: RECIST v1.1: ORR of 38% (n=29) with 11 durable objective responses including 3 complete responses and 8 partial responses (1 unconfirmed); median progression-free survival of 8.1 months and disease control rate of 58.6%.

mRECIST: ORR of 43% (n=28) with 12 durable objective responses including 3 complete responses and 9 partial responses (1 unconfirmed); median progression-free survival not reached and disease control rate of 60.7%. Further analyses of samples from patients who responded to treatment (small n) indicate preliminary association between response and biomarkers of IL-27. These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC.

Coherus plans to evaluate the combination of casdozo/toripalimab-tpzi(Coherus? anti-PD-1 antibody)/bev in future clinical trials. Poster presentation details: Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VegF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) Poster Board number: B15 Abstract number: 470; Date and Time: January 19, 2024, 12:30 ?

2:00 pm PT; Presenter: Daneng Li, MD; Location: Level 1, West Hall, Moscone West.