SHR-1701 is a novel therapeutic agent currently under investigation for cancer treatment. This drug represents an advancement in fighting cancer by engaging the body’s own immune system. It offers a new avenue for patients, particularly those with advanced or difficult-to-treat cancers.
What SHR-1701 Is
SHR-1701 is a “bifunctional fusion protein,” an engineered molecule designed to perform two distinct functions simultaneously. A “fusion protein” combines components from different proteins into one new, larger protein. This unique design allows SHR-1701 to target two specific molecules: programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-β).
PD-L1 is a protein found on the surface of some cancer cells and immune cells, which can act as a “cloak” for tumors, preventing immune cells from recognizing and attacking them. TGF-β is a signaling molecule involved in various cellular processes, and in the context of cancer, it can suppress the immune system and promote tumor growth and spread. By combining these two targeting abilities, SHR-1701 is designed to address multiple ways cancer evades the body’s defenses.
How SHR-1701 Fights Cancer
SHR-1701’s dual targeting mechanism fights cancer by unleashing the immune system and disrupting the tumor’s protective environment. It blocks PD-L1, a strategy known as immune checkpoint blockade. Normally, PD-L1 on cancer cells binds to a protein called PD-1 on immune T-cells, effectively putting the brakes on the immune response and allowing cancer cells to escape detection and destruction. By blocking PD-L1, SHR-1701 removes this “brake,” enabling T-cells to become active and target the cancer cells more effectively.
Simultaneously, SHR-1701 targets and neutralizes TGF-β. In the tumor microenvironment, which is the complex network of cells and molecules surrounding a tumor, TGF-β can create an immunosuppressive shield that actively prevents immune cells from reaching and attacking the cancer. It does this by promoting the growth of regulatory T cells, which suppress immune responses, and by inhibiting the function of effector T cells and natural killer (NK) cells, which are crucial for killing cancer cells.
By blocking TGF-β, SHR-1701 helps to dismantle this shield, making the tumor microenvironment more favorable for immune attack. This dual action is designed to create a synergistic effect, meaning the combined impact of blocking both PD-L1 and TGF-β is potentially greater than blocking either pathway alone.
Cancers Treated by SHR-1701
SHR-1701 is currently being investigated for its potential in treating specific types of cancer. One primary area of focus is recurrent or metastatic cervical cancer. Recurrent cervical cancer refers to cancer that has returned after initial treatment, while metastatic cervical cancer indicates that the cancer has spread beyond its original site. These forms of cervical cancer often present limited treatment options after standard platinum-based therapies have failed.
SHR-1701 is also being explored for HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Gastric cancer originates in the stomach, and GEJ adenocarcinoma arises in the area where the esophagus meets the stomach. Being “HER2-negative” means that these tumors do not have an overexpression of the HER2 protein, which is a common target for some other cancer drugs. The unique mechanism of SHR-1701, by modulating both immune checkpoints and the tumor microenvironment, makes it a candidate for these specific cancers where current treatments may have limitations or where a dual-action approach could offer an advantage.
Real-World Study Findings
Clinical studies of SHR-1701 have shown promising results across various advanced solid tumors, including the specific cancers it is being investigated for. In a phase I study involving patients with recurrent or metastatic cervical cancer who had previously undergone platinum-based therapy, SHR-1701 monotherapy demonstrated encouraging anti-tumor activity. The objective response rate, which measures the percentage of patients whose tumors significantly shrink, was 15.6% in this cohort. The disease control rate, indicating patients whose disease was stable or shrinking, reached 50.0%.
The duration of response at six months was 80.0%, suggesting that for those who responded, the benefits were sustained. The median progression-free survival, which is the time patients live without their disease getting worse, was 2.7 months as assessed by RECIST criteria, and 4.1 months when assessed by immune-modified RECIST criteria. The overall survival rate at 12 months was 54.6%.
Regarding safety, SHR-1701 has generally shown a manageable profile. In the cervical cancer study, grade 3 or 4 treatment-related adverse events were reported in 34.4% of patients, with no treatment-related deaths occurring. In a phase 3 study for HER2-negative gastric/gastroesophageal junction adenocarcinoma, SHR-1701 combined with chemotherapy demonstrated a statistically significant and clinically meaningful benefit in overall survival. Furthermore, SHR-1701 appeared to reduce the incidence of chemotherapy-associated myelosuppression, which includes decreased platelet count, neutrophil count, and white blood cell count. These findings support the continued development of SHR-1701 as a potential treatment option.