FDA Approves the Roll-Over Combination Study with Checkpoint Inhibitor Immunotherapies to Allow Continued Access to BriaVax™ in Patients with Advanced Breast Cancer

The FDA has approved the roll-over combination study of the investigational breast cancer vaccine, BriaVax™ with pembrolizumab {Keytruda; manufactured by Merck & Co., Inc. or ipilimumab {Yervoy; manufactured by Bristol-Myers Squibb Company for patients previously treated with BriaVax™ from the ongoing Phase I/IIa Clinical Trial in Advanced Breast Cancer.

BriaVax™ is a whole-cell breast cancer vaccine genetically engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system by allowing the body to recognize and eliminate cancerous cells by inducing tumor-directed T cell and potentially antibody responses.

This roll-over combination study allows the patients who did not respond to BriaVax™ (monotherapy) treatment to be treated and continue to receive the potential clinical benefits of the vaccine in combination with either pembrolizumab or ipilimumab. This approach is based on the hypothesis that both pembrolizumab and ipilimumab may improve the anti-tumor activity of vaccine in patients with advanced breast cancer. Safety and efficacy data will be evaluated.

“We are very excited to evaluate the effects of BriaVax™ with other approved anti-tumor immunotherapeutic agents. We expect this study to extend and potentiate the clinical benefits of BriaVax™ in advanced breast cancer patients,” stated Dr. Williams, BriaCell’s President & CEO in a press release. “We look forward to expanding our clinical study and exploring potential immunotherapy partnerships with leading pharmaceutical companies in the future, and we are pleased with the FDA decision,” Dr. Williams added.

The clinical investigators will work closely with Cancer Insight, LLC, BriaCell’s contract research organization, to manage the clinical and regulatory aspects of the clinical trial for the roll-over combination study of BriaVax™ on behalf of BriaCell. More information on the roll-over combination study of BriaVax™ with either ipilimumab or pembrolizumab will be available on ClinicalTrials.gov (Study identifier: BRI-ROL-001).

Manufactured by Merck & Co., Inc., KEYTRUDA® (pembrolizumab) is a prescription medicine that may treat certain cancers by working with the immune system. It has been approved for the treatment of a number of cancer indications excluding breast cancer.

Manufactured by Bristol-Myers Squibb Company, YERVOY® (ipilimumab) is a prescription medicine used in adults and children 12 years and older to treat melanoma (a kind of skin cancer) that has spread (metastatic) or cannot be removed by surgery (unresectable). It is a monoclonal antibody that works to activate the immune system and enabling them to recognize and destroy cancer cells.

BriaVax™ is a whole-cell breast cancer vaccine genetically engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system. Previously, a small Phase I study documented very prompt and near complete regression of metastatic breast cancer deposits in the breast, lung, soft tissue, and even the brain.

The ongoing open-label Phase I/IIa study will evaluate BriaVax™ in up to 40 advanced breast cancer patients. This trial is listed in ClinicalTrials.gov as NCT03066947. The trial is being conducted along with the co-development of BriaDx™, our companion diagnostic test. The interim data for the first 10 patients is expected by the first quarter of 2018.

BriaCell is an immuno-oncology focused biotechnology company developing a targeted and safe approach to the management of cancer. BriaCell’s mission is to serve late-stage cancer patients with no available treatment options.

Immunotherapy has come to the forefront of the fight against cancer, harnessing the body’s own immune system in recognizing and selectively destroying the cancer cells while sparing normal ones. Immunotherapy, in addition to generally being more targeted and less toxic than commonly used types of chemotherapy, is also thought to be a strong type of approach aimed at preventing cancer recurrence.

The results of two previous Phase I clinical trials (one with the precursor cell line not genetically engineered to produce GM-CSF and one with BriaVax™) have been encouraging in patients with advanced breast cancer. Most notably, one patient with metastatic breast cancer responded to BriaVax™ with substantial reduction in tumor burden including lung and brain metastases. The company is currently conducting a Phase I/IIa clinical trial for BriaVax™ in patients with advanced breast cancer whose disease has progressed following at least one prior treatment course.

This trial is listed in ClinicalTrials.gov as NCT03066947.  The trial is being conducted along with the co-development of BriaDx™, our companion diagnostic test. The interim data for the first 10 patients is expected by the first quarter of 2018.

In a previous Phase I setting, a patient with metastatic breast cancer responded to BriaVax™ with objective reduction in tumor burden. To expand on this finding, after updating the clinical protocol of the original investigational new drug (IND) application, an open-label Phase I/IIa clinical trial enrolling up to 40 late stage breast cancer patients with recurrent and/or metastatic disease has been launched. Patients will be administered BriaVax™ every two weeks for the first month of treatment, then monthly up to one year.

The primary objective of the Phase I/IIa clinical trial is to evaluate the safety of BriaVax™ in study subjects, and the principal secondary objective is an evaluation of the tumor size reduction. Tumor response will be monitored every three months during the study. The trial will also evaluate progression-free survival (PFS) and overall survival (OS).

For additional details regarding the clinical trial, please visit:
https://www.clinicaltrials.gov/ct2/show/NCT03066947

Novartis garners first ever FDA approval for a CAR-T cell therapy, Kymriah(TM), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice

Novartis announced today that the US Food and Drug Administration (FDA) has approved Kymriah(TM)(tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient’s own T cells to fight cancer. Kymriah is the first therapy based on gene transfer approved by the FDA.

“At Novartis, we have a long history of being at the forefront of transformative cancer treatment,” said Joseph Jimenez, CEO of Novartis. “Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care.”

The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.

There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years [2], [3].

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

“This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients’ lives,” said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine, who is a pioneer of this new treatment. “Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types.”

In close collaboration with Novartis and Penn, Children’s Hospital of Philadelphia (CHOP) was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial.

“Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and durable remission in children and young adults with relapsed or refractory B-cell ALL,” said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia (CHOP). “We’ve never seen anything like this before and I believe this therapy may become the new standard of care for this patient population.”

Novartis is committed to ensuring eligible patients have access to Kymriah, and is working to ensure payers understand the value of Kymriah and provide coverage for patients. To address the unique aspects of the therapy, Novartis has also developed various patient access programs to support safe and timely access for patients. Novartis is also providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured.

Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.

FDA Halts Three Multiple Myeloma Studies Evaluating Merck’s KEYTRUDA®

Merck known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on KEYNOTE-183, KEYNOTE-185 and KEYNOTE-023, three combination studies of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in the blood cancer multiple myeloma.

This decision follows a review of data by the Data Monitoring Committee in which more deaths were observed in the KEYTRUDA arms of KEYNOTE-183 and KEYNOTE-185 and which led to the pause in new patient enrollment, as announced on June 12, 2017. The FDA has determined that the data available at the present time indicate that the risks of KEYTRUDA plus pomalidomide or lenalidomide outweigh any potential benefit for patients with multiple myeloma. All patients enrolled in KEYNOTE-183 and KEYNOTE-185 and those in the KEYTRUDA/lenalidomide/dexamethasone cohort in KEYNOTE-023 will discontinue investigational treatment with KEYTRUDA.

This clinical hold does not apply to other studies with KEYTRUDA.

The following studies have been placed on full clinical hold:

  • KEYNOTE-183: “A Phase III study of Pomalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in refractory or relapsed and refractory Multiple Myeloma (KEYNOTE-183).”
  • KEYNOTE-185: “A Phase III study of Lenalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in newly diagnosed and treatment naïve Multiple Myeloma (KEYNOTE-185).”

The following study has been placed on partial clinical hold:

  • KEYNOTE-023 Cohort 1: “A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination with Backbone Treatments for Subjects with Multiple Myeloma (KEYNOTE 023).” Cohort 1 of KEYNOTE-023 evaluated KEYTRUDA (pembrolizumab) in combination with lenalidomide and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).

“Patient safety is Merck’s primary concern, and we are grateful to the study investigators and patients involved in these studies for their commitment to this important research,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Merck’s development program for KEYTRUDA, spanning more than 30 different tumor types, has one priority: helping patients suffering from cancer.”

For more information about Merck’s oncology clinical trials, visit www.merck.com/clinicaltrials.

Photo-Bombing Cancer

When Kerstin Stenson, MD, describes the innovative technique she is helping develop to fight cancer, it seems like she’s describing a Tom Clancy military espionage novel.

Stenson is treating patients with photoimmunotherapy, PIT for short, an experimental technique that combines the immune system’s ability to target cancer cells precisely with laser energy’s ability to destroy those cells. Like a high-tech weapon in a Clancy thriller, PIT delivers extremely precise, lethal payloads with minimum collateral damage.

“This treatment is so unique and promising because its cancer cell-killing power is so selective and immediate,” says Stenson, director of Rush University Medical Center’s Head and Neck Cancer Program. “It really is just like a guided missile.”

Cold war spy novels like Clancy’s that celebrate military technology aren’t Stenson’s first fiction choice, but she appreciates their parallels to her work when it comes to developing new weapons to fight an old enemy. Just as a hero needs to defeat the bad guys while also saving the hostages, PIT meets the fundamental challenge in defeating cancer: balancing the ability to destroy cancer cells while limiting the damage to surrounding tissue.

Delivering a payload, aiming a laser, and setting off an explosion

Photoimmunotherapy expands upon an existing therapy called photodynamic therapy, a two-step process that starts with a patient being injected with a specialized drug, called a photosensitizer, that’s designed to accumulate in and near a cancerous tumor. Then doctors beam specific wavelengths of light at the tumor, causing the absorbed photosensitizer to produce a form of oxygen which kills nearby cells.

But in photoimmunotherapy, the photosensitizer is combined with a laboratory-produced antibody — called a monoclonal antibody — that specifically targets and binds with receptors found only on the surface of head and neck cancer cells. Administered intravenously, the photosensitizer/antibody combination — referred to as a “payload drug” — circulates throughout the patient’s body, but only latches onto head and neck cancer cells.

The next day, Stenson affixes tiny, laser-optic fibers near the surface of the tumor. If the tumor is difficult to reach, she threads the fibers through small catheters directly into the tumor. Then the laser light energy is beamed through the fibers, hitting the photosensitizer target. The laser sets off molecular-level explosions that weaken the cancer cell walls, allowing water molecules contained in the surrounding tissue to rush in until cancer cells burst.

“Almost immediately, you can see the tumor start dying. It turns white and melts away,” Stenson says. Because the payload drug remains inert unless activated by a specific wavelength of light that doesn’t damage human tissue, destroying the cancer cells causes almost no damage to surrounding cells. “The drug/dye combination (the monoclonal antibody combined with the photosensitizer) is not toxic until activated by near infrared light, thus is very safe from a systemic perspective,” Stenson explains.

By comparison, patients treated with conventional photodynamic therapy, PIT’s predecessor, must avoid strong sunlight for several months because tiny amounts of photosensitizer that remain in their systems could be activated by the sunlight, causing a severe sunburn.

PIT provides option after other treatments have failed

Stenson is leading a clinical trial that is testing the safety and effectiveness of PIT for patients whose head and neck cancer is not responding to radiation or chemotherapy, or when surgery is not feasible due to a tumor’s hard to access location. “Getting inside the cancer cell means we can get systemic treatment locally more than any other treatment,” she says, adding that PIT is the most exciting and promising therapy she has ever been involved with.

The study is sponsored and funded by Aspyrian Therapeutics, the biotechnology firm that created the monoclonal antibody conjugate, RM-1929, and secured the exclusive license for the technology from the National Cancer Institute, which developed the original photoimmuno therapy technology.

“Photoimmunotherapy is a first-in-class treatment platform designed to provide an option for patients whose head and neck cancer has failed standard of care treatments,” says Merrill Biel, MD PhD, who developed the PIT clinical trial program and recruited Stenson and Rush to be one of the five participant sites in the safety and effectiveness study. “Chemo has not worked, radiation has not worked. Surgery can’t help them.” Rush is the only center in Illinois offering this treatment.

He asked Stenson to participate because of her national reputation in the field of head and neck cancer care. “She is known across the country for developing cutting-edge, innovative and life-saving treatments that advance our field and offer hope to patients who’ve run out of options,” he says. “Her expertise and insight have been a great addition.”

PIT could be treatment for other types of cancers.

Beyond the exciting potential of PIT as a very effective therapy for head and neck cancer, it has great potential for treating other forms of cancer and as a combination therapy with immune-modulation chemotherapy. “We hope that once we prove the safety and effectiveness of this treatment specifically for head and neck cancer, the photosensitizer could be combined with immune stimulating drugs that target other forms of cancer,” Stenson says.

Because PIT therapy seems to work so precisely and quickly, there also may be great potential in combining the approach with surgery. Even when a cancer surgeon successfully removes a cancerous tumor, some cancer cells invariably remain in the surrounding tissue and are a danger to spread, which is why cancer surgery often is followed by chemotherapy. Since surgery makes those areas temporarily accessible, PIT’s one-two punch of light energy-activated targeted therapy might greatly reduce the chance that the cancer redevelops.