A Randomized Phase 2 Study of Casdozokitug in Combination With Toripalimab Plus Bevacizumab in Participants With Unresectable and/or Locally Advanced or Metastatic Hepatocellular Carcinoma

Trial Details

Sponsor: Coherus Biosciences, Inc. (industry)

Phase: 2

Start date: Dec. 20, 2024

Planned enrollment: 72

Trial ID: NCT06679985

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More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: CHS-388 (SRF388, casdozo, casdozokitug)

HealthScout AI Analysis

Goal: Evaluate the safety and antitumor activity of adding the anti–IL‑27 antibody casdozokitug to toripalimab plus bevacizumab in unresectable/locally advanced or metastatic hepatocellular carcinoma (HCC), and determine the recommended dose of casdozokitug for this combination.

Patients: Adults with unresectable, locally advanced or metastatic HCC not amenable to curative surgery or locoregional therapy, or with progression after such therapies. At least one measurable, untreated lesion per RECIST v1.1 is required. Patients must be systemic therapy–naïve for HCC and without fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma/HCC histologies. Those with moderate/severe ascites or uncontrolled effusions requiring recurrent drainage are excluded.

Design: Randomized phase 2 study with three arms and approximately 72 participants. Allocation is randomized to compare two dose levels of casdozokitug added to toripalimab plus bevacizumab versus the active comparator of toripalimab plus bevacizumab alone. Primary purpose is treatment; safety and efficacy assessed by investigator review.

Treatments: Arm A: lower-dose casdozokitug plus toripalimab plus bevacizumab. Arm B: higher-dose casdozokitug plus toripalimab plus bevacizumab. Arm C: toripalimab plus bevacizumab (active comparator). Casdozokitug (CHS‑388; SRF388) is a first‑in‑class human IgG1 monoclonal antibody targeting interleukin‑27 by binding the p28 subunit, blocking IL‑27 receptor signaling and aiming to reverse IL‑27–mediated immunosuppression to enhance T and NK cell antitumor activity. Early phase studies across solid tumors, including HCC and NSCLC, have shown signals of activity as monotherapy and in combination with PD‑1 inhibitors, with confirmed partial responses in PD‑(L)1–refractory squamous NSCLC and FDA Fast Track designation in liver cancer. Safety to date has been generally favorable with mostly grade 1–2 adverse events (fatigue most common) and no dose‑limiting toxicities observed up to 20 mg/kg in early trials. Toripalimab is a PD‑1 inhibitor used to restore antitumor immune responses. Bevacizumab is an anti‑VEGF antibody that inhibits angiogenesis and is a standard component of first‑line immunotherapy-based regimens in HCC.

Outcomes: Primary outcomes are objective response rate per RECIST v1.1 by investigator and incidence of treatment-emergent adverse events. Secondary outcomes include objective response rate by HCC mRECIST; duration of response by RECIST v1.1 and mRECIST; progression-free survival by RECIST v1.1 and mRECIST; disease control rate by RECIST v1.1 and mRECIST; overall survival; and pharmacokinetics of casdozokitug (Cmax, Cmin, Tmax). Assessments are planned for up to approximately 2 years for efficacy and up to approximately 27 months for safety, with PK sampling up to approximately 25 months.

Burden on patient: Moderate. Participants will receive intravenous therapies requiring regular infusion visits and safety monitoring. Imaging at typical 6–12 week intervals for RECIST and mRECIST assessments, along with laboratory tests, will be required. The investigational arms will include pharmacokinetic blood draws over multiple cycles and potentially additional safety labs, increasing visit time and needle sticks compared with the comparator arm. No mandated biopsies are specified, but exclusion criteria and fluid management may necessitate imaging and clinical evaluations. Travel and time commitments are greater than standard single‑agent therapy due to combination infusions and PK sampling, but remain typical for a multicenter phase 2 combination immunotherapy study.

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