OncoSec, UCSF, and Merck Initiate a Landmark Phase IIb Combination Trial of Breakthrough Drug KEYTRUDA® And ImmunoPulse to Treat Metastatic Melanoma
OncoSec Medical is changing the cancer experience. Today changes the course of OncoSec as we announced a collaboration with the University of California San Francisco (UCSF), to evaluate the safety, tolerability and efficacy of the combination of Merck’s anti-PD-1 drug, KEYTRUDA® (pembrolizumab), and OncoSec’s ImmunoPulse therapy (intratumoral IL- 12), in a phase II metastatic melanoma study with patients non-responsive to KEYTRUDA®. This is an Investigator Sponsored Trial led by renowned Oncologist Dr. Alain Algazi at the prestigious University of California San Francisco and supported by OncoSec Medical and Merck Research Labs. This powerful combination is expected to treat the larger population of approximately 70% of the patients for which it is not currently effective by one of the most exciting breakthrough drugs in treatment of cancer.
For the last year, OncoSec has been focused on the the tremendous unmet medical need of metastatic melanoma patients, who don’t respond to PD-1/PDL1 therapeutics. Unfortunately, these patients represent approximately 70% of metastatic melanoma patients. OncoSec data – both preclinical and clinical – demonstrates that intratumoral Immunopulse therapy with IL–12 drives an increase in TILs. Based on these data, we have proposed that Immunpulse IL-12 will “convert” anti-PD-1 non-responders into responders, leading to potentially enhanced clinical efficacy of PD-1. The field of immunotherapy is beginning to focus on where we’ve been for the last year – an awareness that PD-1 non-responders constitute a tremendous unmet medical need and business opportunity.
This collaboration is significant because of the speed of being able to get into a clinical trial to test our hypothesis and as a critical and positive step in the development of IL-12 immunotherapy. I believe this is yet another sign giving validation of the value of intratumoral immunotherapy and combinatorial approaches as part of an overall therapeutic regimen to treat cancer.
Key Highlights:
Only minority of patients respond to KEYTRUDA®
Patients who do not respond to KEYTRUDA® do not have immune cells (i.e. the correct TILs) already present in the tumor
ImmunoPulse has the potential to bring the correct immune cells into the tumor
Thus, ImmunoPulse has the potential to address the approximately 70% of patients who do not respond to KEYTRUDA®
ImmunoPulse, uses plasmid DNA that encodes for IL-12 and delivers it directly into the tumor using a proprietary delivery device. Preclinical and clinical data suggest that local delivery and expression of IL-12 with ImmunoPulse promotes tumor immunogenicity and increases tumor-infiltrating lymphocytes (TILs). Over 70 patients have been treated with ImmunoPulse, and no serious drug related toxicities have been reported to-date, which demonstrates the strong safety profile of this therapy.
ImmunoPulse has the potential to be the ultimate combination therapy with a new class of immunotherapies called, checkpoint inhibitors. Merck’s recently approved KEYTRUDA® (pembrolizumab), is the first anti-PD-1 (programmed death receptor-1) checkpoint therapy approved in the United States for metastatic melanoma, based on strong Phase 2 data, that showed a 24 percent overall response rate. Despite the deserved excitement, there still remains an unmet medical need for the approximately 70 percent of patients who do not respond to this drug. New data suggest that 24% of the Melanoma patients who best respond to KEYTRUDA® are those who already have immune cells (i.e. TILs) in the tumor, and the approximately 70 percent of the patients that have little or no immune cells in the tumor do not respond to KEYTRUDA®. Since IL- 12 promotes tumor immunogenicity and increases the number of TILs in the tumor, the combination of our therapy to increase TILs in the tumor, and KEYTRUDA® which activates these cells to kill the tumor, present an exciting landmark study to address the vast majority of the metastatic melanoma patients, as well as, have profound implications on many other tumor indications.
Dr. Alain Algazi, Principal Investigator at UCSF said, “Merck’s PD-1 antibody, KEYTRUDA®, takes the brakes off of the anti-melanoma immune responses. ImmunoPulse with IL-12 has the potential to bring immune cells and signals into the tumor so that, when KEYTRUDA® takes the brakes off the immune response, the results could be devastating for the tumor and great for our patients, allowing us to potentially use this combination approach to address a much larger population of patients with aggressive cancer then with KEYTRUDA® alone.”
Dr. Robert Pierce, Chief Scientific Officer, stated, “There is a strong rationale for combining a treatment like ImmunoPulse, which increases TILs, with a T cell checkpoint therapy like KEYTRUDA, to improve anti-tumor efficacy in low-TIL melanoma patients, which make up approximately 70% of the metastatic melanoma patients”
“We are excited and proud to announce this collaboration with Dr. Algazi and UCSF with support from Merck. The achievement of this milestone marks the first clinical trial to evaluate the combination of an anti-PD-1 antibody with an intratumoral therapy using electroporation,” commented Punit Dhillon, President and CEO of OncoSec. “Over the course of the last year, OncoSec has continually stated the need to evaluate intratumoral therapies that have the ability to convert the anti-PD-1 non-responder population to responders. We believe the combination of OncoSec’s ImmunoPulse and checkpoint inhibitors holds significant promise for the treatment of melanoma and other cancers. The caner immunotherapy market is expected to expand up to $35 billion in the next 10 years. Intralesional therapies have the potential to gain a significant portion of this market share.”
This Phase II clinical trial will be conducted as a multicenter Investigator Sponsored Trial (IST), with UCSF and Dr. Alain Algazi as the sponsor. Merck will supply pembrolizumab, and OncoSec will provide electroporation devices and plasmid IL-12. Enrollment is expected to begin in Q1 2015.
About Checkpoint Inhibitors and Combination Approaches
Checkpoint inhibitors have shown promise in a hard-to-treat cancer such as metastatic melanoma. The objective response rate (ORR) with checkpoint inhibitors, like Yervoy (anti-CTLA-4) or Keytruda (anti-PD-1), is in the 10-40% range. There is an obvious need to improve responses and address the needs of the remaining melanoma patients who do not respond to these therapies, thus interventions that complement checkpoint inhibitors are needed.
Mechanistically, checkpoint inhibitors allow the immune cells to recognize and kill the tumors, however, if there are no immune cells already present in the tumor then these checkpoint inhibitors may not be effective. Therefore checkpoint inhibitors may be helped by combining with agents that enhance the infiltration of immune cells into the tumor. It is widely believed and demonstrated in pre-clinical studies (and maybe in early clinical studies) that combining checkpoint inhibitors with complementary immune therapies that can engage a broader immune response could lead to increased efficacy. Of equal importance, is to find potential combination therapies that not only have the potential to improve efficacy, but also pose minimal risk in increasing potential immune- related toxicities.
About KEYTRUDA®
KEYTRUDA is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established.
About metastatic melanoma
Skin cancer is one of the most common types of cancers diagnosed in the United States, with an estimated 2 million new cases annually. Melanoma is the most deadly type of skin cancer, leading to 75% of all skin cancer related deaths due to systemic metastatic spread. Of the 76,000 new Melanoma diagnoses estimated to occur in 2014, approximately 12% will have progressed to stage III or IV melanoma already with a 5- year survival rate of only 15%. Even today, treatment options for melanoma remain limited.
Alain Algazi, M.D. Melanoma Specialist
Dr. Alain Algazi, an oncologist, is a skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center. He treats patients with high- risk and advanced melanoma as well as those with extensive squamous cell and merkel cell carcinoma of the skin. These trials give patients access to new medications, including drugs called BRAF inhibitors that cause melanoma tumors to shrink in a majority of patients treated. He is looking for ways to improve the effectiveness of these medications.
Algazi earned a medical degree at the UCLA School of Medicine and completed an internal medicine residency at UCLA Medical Center. He completed a fellowship in hematology and oncology at UCSF. He is a member of the American Society of Clinical Oncology and American Association for Cancer Research. He is a clinical instructor at UCSF.
About Merck
Merck & Co., Inc. provides various health solutions through its prescription medicines, vaccines, biologic therapies, animal health, and consumer care products worldwide. The companys Pharmaceutical segment offers human health pharmaceutical products, such as therapeutic and preventive agents for the treatment of human disorders in the areas of cardiovascular, diabetes and obesity, respiratory, women’s health and endocrine, inflammatory and infectious diseases, oncology, ophthalmology, immunology, infectious diseases, and others. This segment also provides vaccines, including preventive pediatric, adolescent, and adult vaccines. Its Animal Health segment discovers, develops, manufactures, and markets animal health products comprising vaccines, antibiotics, and anti-inflammatory drugs for respiratory diseases, as well as products for the treatment of fertility disorders. The company was founded in 1891 and is headquartered in Whitehouse Station, New Jersey.
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