The phase 2 trial of porustobart plus tislelizumab showed antitumor activity and manageable safety in heavily pretreated MSS metastatic colorectal cancer.
Antitumor activity and a manageable safety profile were observed with the combination of porustobart (HBM4003) and tislelizumab-jsgr (Tevimbra) in patients with heavily pretreated, non–liver-metastatic, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), according to findings from a phase 2 trial (NCT05167071).1
Porustobart is a next-generation, fully human, heavy-chain–only anti–CTLA-4 antibody discovered and developed using the HCAb Harbour Mice platform. It is the first fully human heavy-chain–only antibody to enter global clinical development.
Among 23 evaluable patients in the study, the regimen generated an objective response rate (ORR) of 34.8%, including 8 partial responses. The disease control rate was 60.9%. The median progression-free survival was 4.2 months. All patients enrolled (n = 24) had received 2 or more prior lines of therapy, and 66.7% of patients had presented with lung metastases at baseline.
“[Porustobart], a next-generation, anti-CTLA-4 antibody discovered through our HCAb Harbour Mice platform, is a direct clinical application arising from this foundational research. The positive results from this phase 2 clinical study mark an important milestone for Harbour BioMed and underscore the therapeutic potential of [porustobart]. We will continue to advance [porustobart] with the goal of delivering transformative immuno-oncology therapies to patients worldwide,” Jingsong Wang, MD, PhD, founder, chairman, and chief executive officer of Harbour BioMed, noted in a news release.
This is an open-label, multicenter clinical trial designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of porustobart in combination with the PD-1 inhibitors toripalimab-tpzi (Loqtorzi) or tislelizumab in patients with advanced neuroendocrine neoplasms (NENs) and other solid tumors, including CRC.2 The trial includes 2 parts. Part 1 was a dose-confirmation portion aimed at determining the recommended phase 2 dose (RP2D) and maximum tolerated dose of porustobart when administered with toripalimab in patients with advanced NENs. Once the RP2D was established, part 2, the dose-expansion portion, further evaluated the safety, tolerability, PK/PD, and early efficacy of the combination in a population of patients with advanced CRC.
Patients received porustobart plus toripalimab for up to 2 years or until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. The study also included a 28-day screening period, post-treatment follow-up at 28 and 84 days after the last dose, and ongoing survival follow-up.
The goal of part 2 of the trial was to establish the optimal dosing strategy and characterize the clinical activity of porustobart in combination with PD-1 blockade as a potential treatment option for patients with advanced solid tumors who have limited available therapies. In part 2, patients received porustobart at 0.3 mg/kg plus tislelizumab at 200 mg every 21 days. ORR served as the primary end point.
The combination of porustobart and tislelizumab was considered generally well tolerated and manageable, with no grade 4 or fatal treatment-emergent adverse effects reported, according to the news release.1 Treatment-related adverse effects occurred in 87.5% (n = 21/24) of patients, most of which were grade 1 or 2 in severity.
The most common AEs, each observed in at least 20% of patients, included liver function test abnormalities, hematologic abnormalities, and pyrexia. Treatment-related serious AEs were reported in 37.5% (n = 9/24) of patients.
