Doing Better on Behalf of Bladder Cancer Patients

Scott Tagawa_IMG_5903On Monday, April 18th, Dr. Scott Tagawa presented promising bladder cancer clinical trial results at the 2016 AACR Annual Meeting.

This phase II study of the antibody-drug conjugate (IMMU-132), demonstrated positive results in a group of adults with metastatic urothelial cancer who did not respond to standard chemotherapies or relapsed after receiving several rounds of the standard chemotherapy treatment regimens.

A form of immunotherapy, antibody drug conjugates are a targeted therapy that leverages the capability of monoclonal antibodies to attach to specific targets on cancer cells. By attaching a drug to the monoclonal antibodies, treatments are able to “hitch a ride” into the cancer cells.

“In this study, eighty-four percent of patients were alive at the nearly one-year mark, compared with an average overall survival of 4-9 months in similar patients who received chemotherapy regimens,” says Dr. Tagawa.

Some side effects were reported, including neutropenia, a low count of a type of white blood cells (neutrophils) in the blood and some diarrhea, but less than would be expected with the free form of the parent drug irinotecan. Irinotecan is a chemotherapy drug mostly used for the treatment of colon cancer. In the body, it is metabolized and breaks down into SN38, which is a more potent molecule. Because of its potency, it would be too toxic to deliver SN38 into the body in general.

IMMU-132 is a drug in which SN38 is linked to an antibody which recognizes Trop2. Trop2 is a protein in the surface of several different types of cells and is over-expressed on many common cancer types, including urothelial cancer. Since the drug shuttles SN38 preferentially into tumors, patients benefit from the potent drug without as many side effects as general chemotherapy.

This drug is also known as Sacituzumab Govitecan, and has already received FDA-breakthrough designation for the treatment of patients with triple negative breast cancer.

The Weill Cornell Medicine clinical trial continues to enroll patients with advanced urothelial cancers (tumors arising from the bladder, renal pelvis, and ureters). For more information about eligibility and enrollment, click here.

What are Cancer Neoantigens? The Link Between Neoantigens and Immunotherapy

By Bishoy Faltas, M.D.

Our immune system has evolved over time to enable us to fight infections. Our bodies need to differentiate between our own cells (self) and cells from bacteria and viruses (non-self) in order to mount an effective attack to eliminate the invaders. In order to do that, our immune system has learned to recognize fragments of foreign proteins, which carry a specific sequence that marks them as “targets” for the immune system. We call these antigens.

Cancer cells thrive because they hide from the immune system, but their disguise is not perfect. Cells typically become cancerous because of changes in their genetic makeup. These same changes can result in proteins that the immune system is able to recognize as foreign. These are called neoantigens, and refer to new cancer antigens that cue the immune system to attack the cancer and eliminate it.

neoantigen[2]
New sequencing technologies enable us to detect new cancer antigens unique to each patient.
The immune system just needs a little help to make this happen. To tip the balance in favor of the immune system, we now use drugs called immune checkpoint inhibitors. These unleash the power of the immune system to attack the tumor. A good way to think about it is as “releasing the brakes” off the immune response. This approach to treatment is very promising for bladder cancer, especially when other treatments have failed to stop the cancer from progressing or metastasizing to other organs.

To understand which patients are most likely to respond to these immune checkpoint inhibitors, we conducted a study examining the neoantigens in bladder cancer patients at Weill Cornell Medicine. Our analyses found many differences in the neoantigens between untreated tumors and advanced tumors that had previously been treated with chemotherapy from advanced chemotherapy-resistant bladder cancers. More details on our findings can be found here:

In the future, we are hoping to use neoantigens as biomarkers that tell us which patients are most likely to respond to specific immunotherapies. A form of precision medicine, this will help us to narrowly tailor our treatment approach to each patient.

Some of our current immunotherapy treatments for people with bladder cancers include:

Cancer: A Wolf in Sheep’s Clothing

Immunotherapy wolf in disguiseCancer cells can be pretty sneaky, altering their make-up or microenvironment to avoid detection by our body’s immune system. As a result, the immune system, which is designed to fight off “invaders,” can’t detect cancer as foreign and doesn’t have its guard up.

Earlier this month, NewYork-Presbyterian Hospital kicked off a new ad campaign highlighting how immunotherapy is working to change just that. Immunotherapy treatments are designed to help activate the immune system and kick it into high gear, helping it fight the very cancer it was previously unable to detect.

New scientific discoveries happening right here at Weill Cornell Medicine are making this possible. Our physician-scientists and researchers at the Meyer Cancer Center have found ways to help the immune system better recognize and destroy cancer cells by designing new immunotherapy drugs, cancer “vaccines,” and combination treatments. Through precision medicine and an individualized approach to cancer care, we are developing new ways to treat cancer more successfully than ever before. And, we’re accomplishing these results with less toxicity.

Over the past decade, the U.S. Food and Drug Administration (FDA) has approved several new immunotherapy drugs for advanced cancers. At the Weill Cornell Genitourinary (GU) Oncology Program, we have greatly contributed to the efforts to obtain FDA-approval for immunotherapies for GU cancers, including kidney cancer, bladder cancer, and prostate cancer.

For kidney cancer, we have been involved in many studies of drugs utilizing the immune system to fight cancer, including the phase 2 clinical trial that formed the basis for the large trial leading to the FDA approval and general availability of nivolumab (Opdivo) for renal cell carcinoma. Nivolumab is an immunotherapy that works by allowing the body’s existing immune system to kill tumors. Our team is now working on ways to improve this drug and other types of drugs.

For bladder and other urothelial cancers, we have been instrumental in the development of several antibodies that can be used with and without chemotherapy. Sacituzumab Govitecan (IMMU-132), an antibody-drug conjugate, has had remarkable preliminary activity. It works by leveraging the immune system and bringing a powerful drug directly to the interior of cancer cells in order to kill them from the inside out. We are continuing to use this drug as well as other immunotherapeutic agents to improve outcomes for patients with these types of cancer.

Based upon several scientific properties, prostate cancer is a good tumor type for immunotherapy, and in fact, the first therapeutic cancer vaccine (used to treat cancer rather than prevent cancer) was approved for prostate cancer. At Weill Cornell Medicine, exploiting the immune system remains a focus in fighting prostate cancer, with a number of ongoing and upcoming clinical trials. Weill Cornell Medicine continues to be a worldwide leader in work with monoclonal antibodies, which are proteins (like a “key”) that very specifically target cancer cells (with a specific “lock” that is not present on normal cells). In particular, our work with antibodies against prostate-specific membrane antigen (PSMA) has led to the development of several targeted therapies for prostate cancer. These antibodies can be linked to powerful radioactive particles or drugs that seek out prostate cancer cells (like a smart bomb). For men with prostate cancer whose PSAs rise despite hormonal therapy, we are leading a study of targeted radioimmunotherapy that aims to prevent metastatic disease. In addition, the antibody itself may be able to generate an immune response in prostate tumors and lead to clearance of circulating tumor cells. We are also working on developing vaccines for men with rising PSAs following surgery or radiation.

We continue to examine many promising, cutting-edge immunotherapies through our robust clinical trial program. Click the below links to learn more about eligibility and open clinical trials across the spectrum of GU cancers:

Open Immunotherapy-Based Clinical Trials

Prostate Cancer

Kidney, Bladder and Urothelial Cancers

To search our complete list of our open clinical trials, click here.