KAHR Bio's DSP107 Combination Shows Promise in Microsatellite Stable Colorectal Cancer at ASCO 2025
核心洞察
KAHR Bio (搜索) will present Phase 2 data on DSP107, a first-in-class bi-specific 4-1BB (搜索) T-cell engager, combined with atezolizumab for third-line microsatellite stable colorectal cancer (搜索) at ASCO 2025.
The combination therapy demonstrated anti-tumor activity and extended survival in patients with liver metastases (搜索), addressing a significant unmet medical need in MSS-CRC (搜索) treatment.
DSP107 uniquely converts CD47 (搜索) signals into 4-1BB (搜索) activation, engaging both innate and adaptive immunity to overcome the immunotherapy resistance typical of MSS-CRC (搜索).
KAHR Bio (搜索) announced that positive results from its Phase 2 dose expansion cohort evaluating DSP107 in combination with atezolizumab will be presented as an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The study focused on patients with third-line microsatellite stable metastatic colorectal cancer (搜索) (MSS-CRC (搜索)), a patient population with limited treatment options and poor prognosis.
Novel Mechanism Addresses Immunotherapy Resistance
DSP107 represents a first-in-class bi-specific 4-1BB (搜索) T-cell engager that utilizes CD47 (搜索) overexpression as a tumor anchor. The drug binds to CD47 expressed on cancer cell surfaces and converts the CD47 signal, which cancer cells use to evade the innate immune system, into a 4-1BB signal that attracts and activates adaptive immune cells, primarily cytotoxic CD8 T-cells.
"This recognition is evidence for the significant potential of this immunotherapy combination to benefit the treatment of MSS-CRC (搜索) patients including those with active liver metastases (搜索), a devastating disease representing an unmet medical need," said Yaron Pereg, Ph.D., Chief Executive Officer of KAHR.
Clinical Trial Design and Patient Population
The MSS-CRC (搜索) dose expansion phase was conducted as an open-label, multi-center trial (NCT04440735) enrolling patients with third-line MSS colorectal cancer. Patients received weekly DSP107 infusions at 10 mg/kg combined with atezolizumab (Tecentriq®) at 1200 mg every three weeks until disease progression. The primary objective focused on determining safety and tolerability, while secondary objectives assessed preliminary efficacy.
Targeting a Challenging Cancer Subtype
Microsatellite stable metastatic colorectal cancer (搜索) represents the majority of colorectal cancer cases and poses significant treatment challenges. Unlike microsatellite instability-high (MSI-H) tumors, MSS-CRC (搜索) exhibits lower tumor mutational burden and demonstrates resistance to immunotherapy approaches. The condition is particularly relevant in colorectal cancer, where over 70% of metastatic patients develop liver metastases (搜索) that highly express CD47 (搜索) in response to first- and second-line chemotherapy treatments.
Previous immunotherapy attempts in colorectal cancer have failed due to the lack of immune cell infiltration in tumors. DSP107's unique mechanism takes advantage of CD47 (搜索) expression to drive immune cells into the tumor microenvironment, potentially overcoming this limitation.
Promising Survival Data
The combination therapy demonstrated anti-tumor activity and extended survival, including in patients with liver metastases (搜索). According to Pereg, updated overall survival data for the combination has continued to improve in 2025 beyond the data published in the abstract, with results to be shared at the ASCO presentation.
The oral presentation, titled "Phase 2 dose expansion study of DSP107, a first-in-class bi-specific 4-1BB (搜索) T-cell engager, with and without atezolizumab in metastatic MSS colorectal cancer patients," will be delivered by Anwaar Saeed, MD, Associate Professor of Medicine at University of Pittsburgh Medical Center and Director of the Gastrointestinal Disease Center at UPMC Hillman Cancer Center (搜索), on June 1, 2025.
Broader Development Program
Beyond colorectal cancer, DSP107 is also being evaluated in a Phase 2 expansion cohort for second- and third-line PD-1 (搜索)-experienced non-small cell lung cancer (搜索), demonstrating the potential broad applicability of this novel immunotherapy approach across multiple solid tumor types.