Experimental drug eliminates aggressive breast, skin cancer in small trial

Medical News Today

2 days ago

Scientists have developed a new cancer drug that can be injected directly into tumors. The treatment, an enhanced CD40 agonist, was successful in its first trial of 12 human participants. Six people in the group saw their tumors shrink, while two participants saw their cancer go completely into remission. The National Institutes of Health project that doctors will diagnose at least 2 million new cancer cases and that 600,000 people will die from cancer in 2025 in the United States.Despite improving cancer death rates, this prediction highlights the need to continue developing more effective treatments. Researchers from Rockefeller University made headway in this area with the completion of their human phase 1 study. They tested a new CD40 antibody drug, 2141-V11, designed to shrink tumors and reduce side effects.The new drug had promising results, shrinking tumors in half the patients and completely eliminating cancer in two cases, while not causing serious side effects. The study appears in the journal Cancer Cell.A new approach to cancer immunotherapyMany cancer treatments exist, and sometimes treatment can be as simple as removing the tumor or lesion for localized cancers. In cases where the cancer is metastatic and has spread, more aggressive treatments are necessary. Some types of more aggressive cancer treatments include: radiation therapychemotherapyhormone therapyimmunotherapy.The American Cancer Society describes immunotherapy as a 'treatment that uses the body's immune system, usually your own, to attack cancer.' There are several types of immunotherapy, such as immune checkpoint inhibitors, CAR T-cell therapy, and monoclonal antibodies. Researchers in the new study focused on immunotherapy — specifically, the CD40 agonist antibody drug class, a type of monoclonal antibody treatment. It works by activating the CD40 receptor and causing an immune system response. According to the study authors, research on CD40 has not been successful in human trials in the past and has caused serious side effects. This led the scientists to create an engineered form of CD40 called 2141-V11. The drug was designed to improve the issues with CD40 and reduce systemic inflammation and liver toxicity. The scientists also decided to inject the treatment directly into the tumor instead of administering it intravenously. For the human study, the researchers recruited 12 participants, and everyone in the group had metastatic cancers including melanoma and breast cancer. The participants ranged from ages 42 to 89.The participants received injections of 2141-V11 into their tumors every 3 weeks, with an increased dosage each time.Promising results with limited toxicityThroughout the 2141-V11 treatments, the researchers monitored the side effects and bloodwork of the participants. They were especially concerned with the participants' platelet count and liver enzymes since these would indicate a treatment-related adverse event (TRAE). By the end of the treatment, ten participants experienced adverse events, and seven experienced TRAEs. However, none of the patients experienced any TRAEs higher than grade 3, and the researchers considered the drug 'well tolerated.' Most of the side effects were mild and included fever and issues where the drug was injected. Three participants had severe adverse events, but the researchers did not consider them TRAEs. One participant had to be hospitalized because of a urinary tract infection, and another had shortness of breath related to chronic heart failure. No serious dose-limiting toxicities occurred, and the participants' liver and platelet levels were stable throughout treatment. Additionally, cancer tumors shrank in six of the participants, and two participants went into complete remission. One of the participants who went into remission had melanoma, and the other had breast cancer. The researchers noted that not only did their tumors shrink, but tumors in the rest of the body disappeared. Wael Harb, MD, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers, spoke with Medical News Today and explained how the cancer drug works.'This drug (2141-V11) is an engineered antibody that flips a key 'ON' switch (CD40) on immune cells inside a tumor,' said Harb, who was not involved in the recent trial. 'It's injected directly into one tumor, where it organizes immune cells into mini lymph nodes called tertiary lymphoid structures (TLS).' 'Those act like on-site training camps that activate cancer-killing T-cells, which then travel through the body to attack tumors that weren't injected,' Harb continued.While he noted that the drug's safety profile was encouraging, he emphasized that larger trials are needed. 'Twelve patients are too few to draw firm safety conclusions across cancers–larger trials are needed and are already underway,' the oncologist cautioned.What is next for 2141-V11?Study author Juan Osorio, MD, director Of Clinical Operations And Translational Immunology at Rockefeller University, spoke with MNT and discussed the future of the research with 2141-V11. 'We look forward to the results of several ongoing phase 2 studies nationwide, targeting difficult-to-treat cancers, such as malignant gliomas, bladder cancer, and prostate cancer,' said Osorio. Osorio mentioned that early data from the phase 2 studies is 'promising,' but it is not a one-size-fits-all solution for people with cancer. 'Not all patients respond, highlighting the need for rational combination strategies to extend the benefit of this therapy,' Osorio shared. Osorio said the team is currently trying to figure out which biomarkers may predict response to CD40 agonists. 'Furthermore, we want to evaluate in larger cohorts whether TLS or other immune spatial interactions are crucial for effective induction of antitumor immunity. Answering these questions will be critical to fully translate this approach into meaningful and durable clinical benefit for patients.'