Porustobart/Tislelizumab Elicits Responses in MSS Metastatic Colorectal Cancer

The anti–CTLA-4 antibody combination achieved an ORR of 34.8%, with 8 partial responses, in patients with pretreated microsatellite-stable mCRC.

Treatment with porustobart (HBM4003), a next-generation, fully human, heavy chain–only anti–CTLA-4 antibody, plus tislelizumab (Tevimbra) elicited positive antitumor activity with a manageable safety profile in pretreated patients with microsatellite-stable (MSS) metastatic colorectal cancer (CRC), according to a press release from the developer, Harbour BioMed.1

The results came from a multicenter, open-label phase 2 trial (NCT05167071) that evaluated the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of porustobart with tislelizumab or toripalimab-tpzi (Loqtorzi) in patients with advanced neuroendocrine neoplasms and other solid tumors.2

Among 23 patients who were efficacy evaluable, the objective response rate (ORR) was 34.8%, with 8 partial responses (PRs); the disease control rate was 60.9%, with 8 PRs and 6 patients achieving stable disease; and the median progression-free survival was 4.2 months.

“The 2025 Nobel Prize in Physiology or Medicine was awarded to 3 immunologists for their groundbreaking discoveries in regulatory T cells [Treg cells] and their role in controlling the immune system. HBM4003, a next-generation anti–CTLA-4 antibody discovered through our HCAb [heavy chain–only antibody] Harbour Mice platform, is a direct clinical application arising from this foundational research,” Jingsong Wang, MD, PhD, founder, chairman, and CEO of Harbour BioMed, said in the press release.1 “The positive results from this phase 2 clinical study mark an important milestone for Harbour BioMed and underscore the therapeutic potential of HBM4003. We will continue to advance HBM4003 with the goal of delivering transformative immuno-oncology therapies to patients worldwide.”

The trial was split into 2 parts: part 1, the dose confirmation part, and part 2, the dose expansion part. A total of 24 patients with MSS metastatic CRC were enrolled in the trial. Enrollment criteria include being 18 years or older or 75 years or younger in part 1 of the trial, having at least 3 months of life expectancy, having at least 1 measurable lesion per RECIST v1.1, and an ECOG performance status of 1 or lower.2 In part 1, patients had histopathology-confirmed diagnoses of advanced or recurrent solid tumors. In part 2A and part 2B, patients had a histopathology-confirmed nonfunctional metastatic neuroendocrine tumor, and in part 2F, patients had histopathology-confirmed metastatic colorectal adenocarcinoma.

Patients who received previous and concomitant treatment with anti–CTLA-4 or anti–PD-(L)1 and anti–PD-L2 treatment within 8 weeks to the start of part 1 or other antitumor treatment were excluded from trial participation. Insufficient recovery from previous treatments, history of other malignant diseases within 5 years of the first dose, and symptomatic, active, or urgent treatment–requiring central nervous system metastasis were also reasons for exclusion.

Treatment consisted of 0.3 mg/kg of porustobart plus 200 mg of tislelizumab every 21 days.

All patients (n = 24) had received at least 2 prior lines of therapy, and lung metastases were observed in 66.7% (n = 16 of 24) of patients.

The primary end points of the trial in part 1 were dose-limiting toxicities, maximum tolerated dose, and recommended phase 2 dose; in part 2, the primary end point was the ORR.

Regarding safety, treatment-related adverse events (AEs) occurred in 87.5% (n = 21 of 24) of patients, with liver function test abnormalities, hematological abnormalities, and pyrexia occurring in at least 20% of patients, with most instances being grade 1 or 2. Treatment-related serious AEs occurred in 37.5% (n = 9 of 24) of patients. No grade 4 or fatal treatment-emergent AEs were observed.

References

1. Harbour BioMed announces positive phase II results for HBM4003 and tislelizumab combination in MSS mCRC. News release. Harbour BioMed. October 22, 2025. Accessed October 27, 2025. https://tinyurl.com/bddpy54f
2. HBM4003 combine with toripalimab in patients with advanced NEN and other solid tumors study. ClinicalTrials.gov. Updated April 27, 2025. Accessed October 27, 2025. https://tinyurl.com/2d8pa2ur