Imfinzi was developed by MedImmune, part of AstraZeneca, and is approved to treat some types of bladder and urinary tract cancers. AstraZeneca is working in collaboration with Celgene, which is carrying out clinical trials to further develop Imfinzi as a possible lymphoma therapy.
How Imfinzi works
Lymphoma is a blood cancer, caused by excessive production of lymphocytes, a type of white blood cell, that can group together to form tumors in various parts of the body.
Imfinzi is a type of immunotherapy, a drug that acts to activate the immune system, allowing the body to recognize and fight cancer cells.
Immune cells called T-cells normally work to recognize and kill infected or abnormal cells, including cancer cells. But the body has immune system checkpoints in place to ensure that T-cells do not destroy healthy cells.
One checkpoint system is the PD-1 (programmed cell death 1) pathway. Healthy cells produce and display a protein called PD-L1 (programmed cell death ligand 1) on the outside of the cell. T-cells produce a receptor (called PD-1) that interacts with PD-L1, sending a message to not attack that cell.
By producing PD-L1, cancer cells can hijack this system to hide from T-cells and evade destruction.
It is an antibody, a protein designed to interact with and block a specific target. It acts by binding to PD-L1, preventing it from interacting with PD-1 and allowing the immune system to recognize and target cancer cells.
Imfinzi is not specific to the cancer cells, however, so it is possible this treatment also removes the immune system checkpoint from healthy cells. One result can be the immune system mistakenly attacking healthy tissues.
Imfinzi in clinical trials
Celgene is running two clinical trials to assess Imfinzi as a treatment for lymphoma and leukemia. However, both have been put on partial hold by the U.S. Food and Drug Administration (FDA) following several unexplained deaths in combination therapy trials involving another PD-1 pathway inhibitor, Keytruda (pembrolizumab). Patients currently enrolled in the trials experiencing a clinical benefit from Imfinzi can choose to continue the treatment, but further recruitment is suspended.
The first trial, MEDI4736-NHL-001 (NCT02733042), is an open-label, multi-center, Phase 1/2 trial to assess the safety and tolerability of Imfinzi alone or in combination with other therapies in both lymphoma and CLL patients. The only trial arm affected by the hold concerns patients receiving Imfinzi in combination with Revlimid (lenalidomide), with or without Rituxan (rituximab) treatment. Unaffected treatment arms include Imfinzi in combination with Imbruvica (ibrutinib) or in combination with Bendeka (bendamustine), with or without Rituxan.
The second trial, MEDI4736-DLBCL-001 (NCT03003520), is a Phase 2 trial assessing the effect of Imfinzi, in combination with Rituxan and CHOP chemotherapy, in previously untreated high-risk diffuse large B-cell lymphoma (DLBCL) patients with or without Revlimid.
Several other ongoing clinical trials are investigating Imfinzi as a lymphoma treatment. For example, MedImmune is running a Phase 1 clinical trial (NCT02549651) to assess Imfinzi alone or in combination with either tremelimumab or AZD9150 in patients with DLBCL.
Imfinzi is administrated as an intravenous infusion over a one-hour period. Side effects commonly include fatigue, muscle and bone pain, constipation, decreased appetite, nausea, swelling, and urinary tract infections. It may, in rare cases, cause potentially fatal side effects, such as problems with organs that include the lungs, liver, intestinal tract, and kidneys.
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