Category: Immunotherapy

Moonshot Summit: Changing Cancer As We Know it

DAVID NANUS, MD

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Photo credit: Ira Fox

On June 29, Weill Cornell Medicine and NewYork-Presbyterian Hospital joined more than 270 institutions across the country in holding a Moonshot Summit. These summits were held in conjunction with Vice President Biden’s Moonshot initiative to fight cancer. On this national day of action, cancer experts throughout our institution, survivors, and advocates came together to share their ideas for increased collaboration and cures.

The summit conversation started with a constructive dialogue about clinical trials and the unfortunate fact that for many cancer types, the “standard of care” chemotherapies are not good enough. At Weill Cornell Medicine and NewYork-Presbyterian, immunotherapies and precision medicine are opening new doors in cancer treatment, but sadly not all patients currently have access to these types of cutting-edge treatments.

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A packed room at the Weill Cornell Medicine/NewYork-Presbyterian Hospital Cancer Moonshot Summit (photo credit: Ira Fox)

Clinical trials may have gotten a bad rap in the past, but they are a powerful tool to access innovative treatments. The speakers agreed that clinical trials should be easily accessible to all patients, but at times there are obstacles. These range from lengthy forms that deter enrollment, to bureaucracy that slows the timeline for opening new clinical trials, to disinterest and concerns about the treatments’ effectiveness. On a global scale, there has been a lack of adult participation in cancer clinical trials, while for children we actually see the opposite trend – very high enrollment. What can we learn from this information?

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(L-R) Dr. Gail Roboz and Dr. Susan Pannullo speaking at the Cancer Moonshot Summit (photo credit: Ira Fox)

One of my colleagues Dr. Gail Roboz wisely stated, “I always tell my patients, be afraid of the disease, not the treatment.” She’s right in that we need to reframe the conversation to focus on making strides in increasing cure rates through new research that leads to new treatment breakthroughs across disease states.

We also talked about access to care. Not all patients are able to get a correct diagnosis quickly. This can be due to a variety of reasons including a lack of access to specialists, living in a rural area, or financial limitations. By increasing government research funding, as well as making it easier for patients to reach quality care, we can remove some of these barriers nationally. If we increase the number of people who are diagnosed with cancer early on, we can increase the cure rates. Additionally, as a country, we need to provide comprehensive care for patients and families and always put the interests of patients first. This includes offering supportive services beyond just the best medical care.

I felt so empowered by my colleagues and our patients’ great ideas about how we can overcome the challenges we face in cancer care. The Cancer Moonshot initiative is giving high hopes to many and will help ultimately change the world of cancer care as our country stands together with common goals and a renewed commitment to collaboration. By bringing everyone together at an event like this, we hear diverse perspectives and glean new insights. The fight against this terrible disease truly unites us all.

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Photo credit: Ira Fox

Immunotherapies for Advanced Bladder Cancers

Cancer MicroscopeImmunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types of bladder cancer immunotherapies currently available:

1. Atezolizumab (brand name Tecentriq) is an FDA-approved immunotherapy for urothelial carcinoma, the most common form of bladder cancer. Atezolizumab is an immune checkpoint blockade or “checkpoint inhibitor.” It selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it. It had been more than two decades since the FDA approved a new bladder cancer treatment.

Atezolizumab is only approved for urothelial carcinoma that has grown or recurred after previous chemotherapy, and we offer this treatment at Weill Cornell Medicine. We are also currently testing another PD-L1 checkpoint inhibitor alone or in combination with another immune checkpoint antibody versus standard chemotherapy through an open phase III clinical trial.

2. Ramucirumab is a monoclonal antibody that binds to the Vascular Endothelial Growth Factor (VEGF) receptor-2. This is a receptor found predominantly on blood vessels. Angiogenesis is a process where vessels grow to feed tumors and blocking this pathway can be helpful at stopping the growth of these vessels, particularly in combination with chemotherapy. We previously completed a randomized phase III trial which demonstrated that patients who got docetaxel (Taxotere) chemotherapy plus ramicurimab had more than twice the tumor shrinkage and double the time until tumor growth compared to docetaxel chemo alone; This study was recently published in the Journal of Clinical Oncology. Based upon our results, we recently opened a phase III trial using this drug in combination with chemotherapy. People who have already received chemotherapy, and those who have received chemo followed by atezolizumab or other checkpoint inhibitors are eligible for this clinical trial.

3. IMMU-132 (also known as Sacituzumab Govitecan) is an antibody drug conjugate 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.

This treatment is a potential good treatment fit for adults with metastatic bladder cancers who have not responded to chemotherapy or who have relapsed after chemotherapy or PL-1/PD-L1 checkpoint inhibitor immune treatment.

Initial positive results in the phase I trial led to a phase II clinical trial that is currently open to enrollment. Learn more about how this drug works in the body and get more information about our open IMMU-132 clinical trial by checking out our recent blog post, “Doing Better on Behalf of Bladder Cancer Patients.”

4. REGN2810 is a monoclonal antibody – a type of protein that works by blocking the programmed death receptor 1 (PD-1), a cell receptor on immune cells that is involved in preventing the immune cells from destroying other cells. Through our open clinical trial, patients with bladder and other urothelial cancers who have received prior treatment with checkpoint inhibitors (such as atezolizumab) can get the combination of the REGN2810 drug with immune boosters.

FDA Approves New Immunotherapy for Bladder Cancer

Cancer LabFor the first time in more than 20 years, today the FDA granted approval to a new treatment for urothelial carcinoma, the most common form of bladder cancer.

Tecentriq, also known as atezolizumab, is an immune checkpoint blockade or inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface. This is the first PD-L1 inhibitor that has been approved by the FDA for any disease.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it, but PD-L1 inhibitors help the body to “see” the cancer and use the immune system to fight it.

This treatment has shown promise for platinum-resistant metastatic urothelial carcinoma – an advanced cancer that does not respond to traditional chemotherapies and which so far has very few other effective therapies.

In the study that ultimately led to atezolizumab’s approval by the FDA, it was shown to be effective at helping unleash the power of the immune system to recognize and attack these tumor cells.

The patients who responded positively to this treatment can do well on it for a long time. This is sometimes referred to as having a “durable response.” Few side effects were seen with this drug and they were mild. Severe side effects were rare and tied to too much immune activity. These study results first led to the FDA granting atezolizumab priority review designation in March 2016 to put it on the fast track for full FDA approval.

Additionally, in this study the investigators identified a correlation between mutational load and response to the drug. This means that when there was a higher concentration of proteins that could be recognized by the body, there was more sensitivity to this immunotherapy.

At Weill Cornell Medicine, we have been involved in the development of several types of immunotherapy and are at the forefront of developing ways to better determine which patients are most likely to respond to treatment. We are conducting research on how mutations and the “mutational load” can lead to the formation of neoantigens and the impact these neoantigens have on immunotherapy response in order to identify the patients most likely to benefit from this therapy.

We’re very excited to be able to offer Tecentriq/atezolizumab to our patients and encourage you to inquire about whether it’s a good fit for you. Additionally, we continue our research with immunotherapy and monoclonal antibodies for patients with urothelial cancer. One open clinical trial is testing whether a single checkpoint inhibitor (targeted at PD-L1) or dual checkpoint inhibitor (targeted at both PD-L1 and CTLA4 – a protein on the T-cell) is more effective against tumors compared with chemotherapy.