HQ Team
August 16, 2025: Phase I clinical trial of the CD40 agonist antibody drug 2141-V11, developed by Rockefeller University’s Jeffrey V. Ravetch lab, has shown improved efficacy and limited side effects on patients with metastatic cancers.
The trial results are published in Cancer Cell. The trial involved 12 patients with various metastatic cancers, including melanoma, renal cell carcinoma, and different types of breast cancer. Six patients experienced systemic tumor reduction, with two achieving complete remission. Notably, the drug’s effect was not limited to injected tumors; tumors in other parts of the body either shrank or were destroyed by immune cells.
“Seeing these significant shrinkages and even complete remission in such a small subset of patients is quite remarkable,” says first author Juan Osorio, a visiting assistant professor in Ravetch’s Leonard Wagner Laboratory of Molecular Genetics and Immunology and a medical oncologist at Memorial Sloan Kettering Cancer Center.
The two patients who achieved complete remission had melanoma and breast cancer, respectively. For instance, a melanoma patient with dozens of metastatic tumors on her leg and foot saw all other tumors disappear after multiple injections into a single thigh tumor. Similarly, a metastatic breast cancer patient with tumors in the skin, liver, and lungs saw all tumors vanish after injection into a skin tumor.
“This effect—where you inject locally but see a systemic response—that’s not something seen very often in any clinical treatment,” Ravetch notes. “It’s another very dramatic and unexpected result from our trial.”
Tissue samples from tumor sites revealed that the drug stimulated immune activity, creating an immune microenvironment within the tumor and essentially replacing the tumor with tertiary lymphoid structures (TLS), which are associated with improved prognosis and response to immunotherapy. The trial found that the drug, when administered via direct tumor injection, caused only mild toxicity, unlike other CD40 drugs that caused serious side effects such as systemic inflammatory responses, low platelet counts, and liver toxicity.
CD40 is a cell surface receptor and member of the tumor necrosis factor (TNF) receptor superfamily. When activated, it prompts the immune system to activate antitumor immunity and develop tumor-specific T cell responses.
In 2018, Ravetch’s lab engineered 2141-V11, a CD40 antibody that binds tightly to human CD40 receptors and is modified to enhance its crosslinking by engaging a specific Fc receptor, making it 10 times more powerful in eliciting an antitumor immune response. Though encouraging , it was found the side-effects were truly debilitating. The Phase I trial aimed to determine the starting clinical dose of the drug and better understand the mechanisms behind its efficacy.
Other cancer treatment drugs
Bladder cancer treatment drug TAR-200
In August 2025, Keck Medicine of USC reported that TAR-200, a novel bladder cancer treatment drug developed by Johnson & Johnson, showed remarkable effectiveness in a clinical trial. The trial involved 85 patients with bladder cancer unresponsive to conventional therapies. Patients were treated with TAR-200 every three weeks for six months, followed by four treatments annually for two years. The results showed that 70 patients achieved cancer remission, with nearly half remaining cancer-free for at least one year. The treatment was well-tolerated with minimal side effects.
The U.S. Food and Drug Administration (FDA) has granted TAR-200 Priority Review for its New Drug Application, meaning the FDA will expedite its review process. The slow-release system used in TAR-200 to deliver cancer-fighting drugs into the bladder offers a new approach for treating bladder cancer.
Rectal cancer treatment drug
In June 2024, a Phase II clinical trial at Memorial Sloan Kettering Cancer Center (MSK) demonstrated that dostarlimab (Jemperli), a checkpoint inhibitor, achieved 100% remission in 18 patients with rectal cancer. All patients had stage II or III rectal tumors with a specific genetic mutation (mismatch repair-deficient or microsatellite instability). They received intravenous dostarlimab every three weeks for six months. Imaging, endoscopy, and other methods showed that the rectal cancer disappeared in all patients, with none experiencing recurrence for up to two years. None of the patients underwent standard treatments such as radiation, surgery, or chemotherapy. In December 2024, MSK reported that 42 patients in the trial achieved 100% remission, with no cancer recurrence for up to four years. The FDA has designated dostarlimab as a breakthrough therapy for rectal cancer.
Myeloma XII (ACCoRd) trial
In May 2025, the results of the Myeloma XII (ACCoRd) trial led by the University of Leeds were published in The Lancet Haematology. The trial tested a treatment regimen for relapsed myeloma patients involving a second autologous stem cell transplant, followed by a combination of thalidomide, dexamethasone, and ixazomib to suppress cancer cells. Ixazomib was then used as a maintenance drug to suppress myeloma cells. The findings showed that this treatment extended disease-free survival by seven months compared to standard treatment.
In April 2023, the results of the AUGMENT-101 trial published in Nature indicated that revumenib, a menin inhibitor, achieved complete remission in approximately one-third of participants with advanced acute myeloid leukemia (AML). Most participants had previously undergone numerous treatments, including stem cell transplants. One participant remained in remission for over 16 months after starting treatment, while 12 others who achieved remission went on to receive stem cell transplants. Of this group, nine remained in remission at the time of the last analysis.
