Pharmaceutical Company Completes Enrollment for Phase 1B Trial for Mesothelioma

ResearcherIf you attended our International Symposium on Malignant Mesothelioma in March of this year, you may recall the buzz of excitement that coursed throughout the scientific sessions. This buzz sparked excitement throughout the entire mesothelioma community, as we discussed advances in science, the needs of those affected by this disease, and the work being done to spur the movement of drugs through the clinical trial process.

Recently, Aduro Biotech issued a press release announcing the completion of enrollment in the Phase 1b clinical trial of its novel immunotherapy, CRS-207. I took the opportunity to call and congratulate Steve Isaacs, the chairman, president, and CEO of Aduro Biotech, on his initial trial results and his plan to move this drug along quickly and offer it globally in the Phase 3 setting.

It is exciting to see plans to jump from a Phase 1b directly to Phase 3 based on what was agreed to be compelling data by the FDA.

Patients treated on the Phase 1b study received 2 doses of CRS-207, a vaccine that utilizes the listeria virus and mesothelin as a target to gain entry into the cell. Patients then went on to receive standard of care pemetrexed/cisplatin every three weeks for 6 courses. If patients were stable or responded to the aforementioned therapy, they were then placed on a maintenance regimen of vaccinations every 8 weeks until progression.

Interim data was presented at a large scientific conference and demonstrated that in the 32 evaluable patients treated on this clinical trial, disease control was observed in 94%, which included a 60% partial response, and 34% experiencing stable disease.

The study will remain open to chemotherapy naive patients (patients who have never received chemotherapy for their mesothelioma) while the plans for the Phase 3 trial continue.

To read more about the CRS-207 study results, click here. To listen to an interview that we held with Steve Isaacs regarding the CRS-207 clinical trial, click here.

A Summary of Mesothelioma Studies from ASCO 2015

MicroscopeBy Hedy Lee Kindler, MD,  University of Chicago

The American Society of Clinical Oncology meeting was held from May 29 – June 2, 2015 in Chicago. About 30,000 attendees from across the world gathered to discuss the latest research advances in all types of cancer, making this the largest, most important oncology meeting of the year. This was a particularly exciting meeting for those of us interested in mesothelioma. I’ve summarized 3 of the most prominent studies below.

MAPS: A randomized trial of pemetrexed, cisplatin with or without bevacizumab. This oral abstract, presented by Dr. Gerard Zalcman on behalf of the French Cooperative Thoracic Intergroup (IFCT), was clearly the star of the show for those of us who care about mesothelioma. This study is important because it is the first randomized trial in over a decade to show that a new drug improves survival in mesothelioma patients. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), which is highly expressed on mesothelioma. Think of it as a drug that targets the blood vessels that feed tumors (angiogenesis). Bevacizumab (the trade name is Avastin) is already FDA approved in multiple cancers, including colon cancer and lung cancer. In the MAPS trial, all 448 patients received standard chemotherapy with pemetrexed plus cisplatin, and half of the patients were randomized to also receive bevacizumab with each dose of chemotherapy. After completing 6 cycles of chemotherapy, patients on the bevacizumab arm also received bevacizumab by itself, every 3 weeks until their cancer started to grow. The time for cancer growth to occur (progression-free survival) was about 2 months longer in the bevacizumab arm (9.59 vs. 7.48 months). Patients treated with bevacizumab also lived almost 3 months longer (18.82 vs. 16.07 months). The addition of bevacizumab did not make patients feel worse (it did not worsen quality of life), although it did cause increased side effects such as bleeding, high blood pressure, and blood clots. Because there was an improvement in survival with the experimental treatment, it is possible that this trial could lead to FDA approval of bevacizumab for mesothelioma—stay tuned!

NGR015: Randomized trial of investigator’s choice of chemotherapy with or without NGR-hTNF. Oral presentations at ASCO are only for the large randomized trials. At most ASCO meetings there are no mesothelioma presentations; this year, there were two! The second oral presentation was by Dr. Rabab Gaafar from Cairo, Egypt on behalf of an international group of investigators. All 400 patients on this trial previously received pemetrexed. They were randomized to receive either NGR-hTNF (another drug that targets angiogenesis) or placebo (sugar water).  In addition, patients could receive chemotherapy either with gemcitabine, vinorelbine, or doxorubicin, or no chemotherapy at all. Unfortunately, the addition of NGR-hTNF to chemotherapy did not affect how long the cancer was controlled, or how long the patients lived. Data is being analyzed to see if certain characteristics might predict which patients might benefit from this drug.

Mesothelin targeted immunotherapy CRS-207, plus pemetrexed/cisplatin chemotherapy. Dr. Raffit Hassan from the National Cancer Institute updated the results of this ongoing trial in a poster presentation. Mesothelin is highly expressed on the surface of mesothelioma. CRS-207 is a vaccine that increases the immune response against mesothelin, and may enhance the activity of chemotherapy. In this study, 2 doses of CRS-207 were given before pemetrexed and cisplatin, as well as after completion of 6 cycles of chemotherapy. Encouraging activity was observed: 60% of patients had tumor shrinkage, and another 34% had disease that did not grow. Thus 94% of patients had disease that was controlled with this experimental vaccine plus chemotherapy. This is much better than would be expected with chemotherapy by itself. Based on these encouraging results, a randomized study to test this combination compared with standard chemotherapy is in development.

Hedy Lee Kindler, MD, an internationally recognized authority on the treatment of mesothelioma, is a Professor of Medicine and the Director of the Mesothelioma and Gastrointestinal Oncology Programs at the University of Chicago. Dr. Kindler is a Past President of the International Mesothelioma Interest Group. She was a member of the Science Advisory Board of the Mesothelioma Applied Research Foundation from 2001-2014, and remains active with the Foundation.  Dr. Kindler chairs the Mesothelioma Subcommittee of the Alliance for Clinical Trials in Oncology, a national cancer clinical trials group. Her research focuses on the investigation of novel agents for the treatment of mesothelioma. Patients from throughout the United States come to Dr. Kindler’s Mesothelioma Clinic at the University of Chicago for her expert care and to participate in her many clinical trials. Dr. Kindler has been listed repeatedly in Best Doctors in America, America’s Top Physicians, America’s Top Doctors for Cancer, and Best Doctors in Chicago.

Meso Foundation Congratulates Dr. Krug on his New Position

Dr. Lee KrugThe Mesothelioma Applied Research Foundation would like to congratulate Dr. Lee M. Krug on his new position with Bristol-Myers Squibb (BMS), which he will be starting in August. He will be joining BMS as the Immuno-oncology Disease Head for Thoracic and GI Malignancies.

Dr. Krug will be leaving his position as an Associate Attending Physician in the Division of Thoracic Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center in New York, New York.

“I promise to remain committed to the foundation and the search for the cure for mesothelioma,” said Dr. Krug.

Dr. Krug has investigated multimodality mesothelioma treatment approaches for patients with early stage malignant pleural mesothelioma. He led a multicenter U.S. trial of induction chemotherapy before extrapleural pneumonectomy, and he has a current study testing the feasibility of chemotherapy followed by pleural radiation. Dr. Krug also has a strong interest in novel therapeutics for patients with more advanced disease. He conducted a phase I trial with a WT-1 peptide vaccine, and he was awarded a grant from the Department of Defense to conduct a randomized phase II trial with this vaccine. He is also the principal investigator of an international, phase III trial of a histone deacetylase inhibitor, vorinostat. Dr. Krug led the committee for the National Comprehensive Cancer Network (NCCN) that established treatment guidelines for mesothelioma.

“Dr. Krug has an unwavering dedication to the mesothelioma field, and I am excited to see what new insight he will bring to the field with his new position at BMS,” stated Melinda Kotzian, Chief Executive Officer at the Meso Foundation.

We congratulate Dr. Krug and wish him the best in his new position.

Updates from ASCO: CRS-207 Vaccine Study Results

MicroscopeAduro BioTech is conducting a clinical trial to test an investigational new immunotherapy for malignant pleural mesothelioma (MPM). This therapy, called CRS-207, is given to a patient in combination with chemotherapy in hopes of encouraging the body’s normal defense mechanisms to fight off the cancer. This trial aims to enroll up to 60 patients at 5 U.S. clinical sites. The company presented data at the American Society of Clinical Oncology (ASCO) conference this week showing that of the 32 patients with MPM treated with CRS-207 and chemotherapy, MPM tumors reduced in size for 19 patients, and tumors remained the same size (stable) in an additional 11 patients. CRS-207 is given prior to and after chemotherapy (cyclophosphamide, pemetrexed and cisplatin) for patients who have not received prior treatment or surgery for their disease.

If you are interested in participating in a clinical trial for this investigational new therapy, please click here.

The 2015 ASCO Annual Meeting, one of the largest oncology meetings of the year, was held from May 29 to June 2 in Chicago, Illinois. The Meso Foundation will be providing more information on studies presented at ASCO in the coming weeks.

Meso Foundation Partners with Insulators Union to Fund Scholarship

Alissa BahrAlissa Bahr, a student at the University of Notre Dame, is this year’s recipient of special funding provided by the Meso Foundation and the International Association of Heat and Frost Insulators (Insulators), for a summer internship at the University of Chicago Medicine. She will be mentored by Drs. Kindler and Salgia, with whom she will work on research and in a clinic setting.

Ms. Bahr is a student at the University of Notre Dame. Her interest in mesothelioma research began last year when she became the recipient of the very first James A. Grogan Fellowship for Excellence. Ms. Bahr has already interned with Dr. Kindler last summer, when she was given the opportunity to participate in all aspects of the program.

“Last summer, I worked on a completely retrospective study, the goal of which was to look at the demographics, genetic data, and treatment response of 56 mesothelioma patients treated by Dr. Kindler,” said Ms. Bahr.

This summer, she will be returning with the goal of transferring the applications of the previous study into a laboratory project, studying the biological effect of different genetic mutations on tissue growth and tumor development. This particular internship, and the guidance she received from Drs. Kindler and Salgia, has solidified Ms. Bahr’s interest in medicine and mesothelioma research.

“I am blessed to have the support of the Meso Foundation and the Insulators Union,” she added.

Ms. Bahr also feels profoundly grateful for this experience because it has allowed her to meet “the best mentor a student could ask for – Dr. Kindler.”

For Dr. Kindler and her team, the feeling is mutual.

“It was such a joy to work with Alissa last summer. She was enthusiastic, energetic, very bright, and eager to learn as much as she could. We are so delighted to have her back with us,” said Dr. Kindler.

The Meso Foundation has been the leader in independent peer-reviewed funding for mesothelioma research. Part of the Foundation’s mission is rooted in providing incentives for young researchers to study mesothelioma. Since awarding its first research grant in 2000, the Meso Foundation has funded over 94 mesothelioma-related projects to date, amounting to more than $9 million.

The insulators, with one in ten of their workers affected by asbestos-related diseases, are at an increased risk of developing mesothelioma. In addition to providing financial support of research, education, patient support, and advocacy, the Insulators have recently founded a tissue bank to collect tissues and/or blood serum from volunteer insulators which is a crucial tool for scientists devoted to mesothelioma research. President Grogan has been a loyal ally and powerful advocate for the meso community, and in 2015, he received the Bruce Vento Hope Builder Award for his work. His explanation of why advancing mesothelioma research is important to the Insulators is as simple as it is powerful.

“If we don’t do this, who will?”