Cancer Treatment Centers of America® (CTCA) clinical investigators based in Phoenix have dosed the first patient in the first-in-human study of NKTR-255, a first-in-class immunotherapy. This Phase I clinical trial is designed to evaluate the safety and tolerability of the experimental treatment as a monotherapy for patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Designed to combine NKTR-255 with multiple targeted antibodies that function through an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism, the study investigators are evaluating the safety and tolerability in adults with in adults with relapsed or refractory multiple myeloma.
Study Addresses Dangerous Blood Cancers
This experimental medicine and study is focused on a significantly deadly pair of diseases. For example, of the approximately 74,200 people diagnosed with NHL annually, nearly 20,000 will die of the disease. And although MM is relatively uncommon, about 32,100 will be diagnosed the disease this year—an estimated 12,960 will die.
And for decades patients diagnosed with these blood cancers have had little options with powerful immune-oncology-based options. This study, led by CTCA and sponsored by industry sponsor Nektar, seeks to change that reality with NKTR-255.
In this Phase I study, to evaluate the safety and tolerability of experimental medicine NKTR-255 along and in combination with daratumumab (Darzalex/Janssen) in patients with relapsed /refractory NHL and MM, patients will receive intravenous NKTR-255 in 21-day treatment cycles. During the Part 1 dose escalation portion of the trial, NKTR-255 will be given as a monotherapy. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, approximately 18 MM or NHL patients who may have received CAR T cell product and have progressed disease (PD) will receive NKTR0-255 and approximately 18 MM patients who previously received daratumumab or other anti-CD38 therapies will receive NKTR-255 and daratumumab.
The study commenced October, 2019 and runs through November, 2021; the protocol calls for up to 82 participants. Inclusion/Exclusion criteria included in Clinicaltrials.gov.
CTCA released one of the first press releases and according to Clinicaltrials.gov they are the only site recruiting at this point–however there are several clinical investigational sites that are planning on conducting this study with industry sponsor Nektar. They include: University of California, San Francisco; H Lee Moffitt Cancer Center and Research institute, Tampa; Winship Cancer Institute, Emory University, Atlanta; University of Michigan, Ann Arbor; Memorial Sloan Kettering Cancer Center, NY; New York Medical College, Valhalla; Duke University, Durham; MD Anderson Cancer Center, Houston; Virginia Cancer Specialists, Fairfax and University of Washington, Seattle.
What is NKTR-255?
Developed by San Francisco Bay Area-based Nektar, NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and expand natural killer (NK) cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which is rapidly cleared from the body and must be administered frequently and in high doses, limiting its utility due to toxicity and convenience of use.
One of the big challenges in treating cancer patients with targeted monoclonal antibodies is that the cancer patients have a deficiency in key effector cells like NK cells that are needed to work with the monoclonal antibodies, reports Nektar. In nonclinical studies, NKTR‑255 exhibited anti-tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function. In a preclinical lymphoma model where single agent daratumumab was ineffective, NKTR-255 treatment, in combination with daratumumab, increased NK cell numbers and activity in bone marrow tissue and enhanced ADCC-mediated tumor cell clearance in the bone marrow compartment.4
In oncology, NKTR-255 is being evaluated in combination with T cell redirection therapies, novel CAR-Ts, anti-HER2 antibodies and anti-CD20 antibodies via an ADCC-focused mechanism in preclinical models of liquid and solid tumors. NKTR-255 is also being evaluated in combination with anti-retroviral and immune modulator therapies through a research collaboration with Gilead.
Cancer Treatment Centers of America (CTCA)
A national, for-profit network of five comprehensive cancer care and research centers and three out-patient care centers, CTCA is headquartered in Boca Rotan, Florida and serves cancer patients throughout the United States. They offer an “integrative approach to care” combining surgery, radiation, chemotherapy and immunotherapy with advancements in precision cancer treatment and supportive therapies designed to manage side effects and enhance quality of life during and after treatment. CTCA offers qualified patients a range of clinical trials that can reveal new treatment options supported by scientific and investigational research. They note in their press releases that their patient satisfaction scores consistently mark among the highest for all cancer care providers.
Originally based in Schaumburg, IL, the corporate office was moved to Florida and renamed Cancer Treatment Centers of America Global Inc. in January, 2015.
Founded by Richard J. Stephenson, who lost his mom to lung cancer, the first step in the process of creation was the acquisition of American International Hospital in Zion, IL in 1988. Back then, Stephenson expanded the hospital services to include a radiation center known as the Mary Brown Stephenson Radiation Oncology Center. This was the first CTCA location. A couple years later they opened up a Tulsa, OK location in the CityPlex Towers and then relocated to a 195,845 square-foot hospital in Tulsa.
By 2004, CTCA purchased the former Parkview hospital in Northeast Philadelphia, PA—investing in renovation including 104,000 square feet and adding an additional 81,000 square feet to support expansion. The Philadelphia site opened in December 2005 and became CTCA’s first hospital on the east coast. By 2008, the Phoenix center was opened—with 210,000 square-foot hospital serving patients mostly from the west coast. By 2012, CTCA’s Atlanta, GA opened for business. Global expansion came with a patient concierge and information office launch in Mexico City. This operation advertises in Latin America, the Caribbean and the Middle East, offering patients in these regions the opportunity to pursue cancer care at one of its U.S. cancer facilities.
CTCA has achieved accreditations from the Joint Commission, American College of Surgeons Commission on Cancer and National Accreditation Program on Breast Cancers. Each center may achieve additional accreditations—for example see the Atlanta, GA facility achievements.
In the summer of 2019, contract research organization (CRO) PPD inked a partnership with CTCA to accelerate patient recruitment in oncology trials, enhancing patient access to potentially life-changing therapies and save time in drug researchers’ quest to find cancer cures. This deal would potentially make PPD’s research services more attractive to sponsors as they could tap into the many patients coming to CTCA centers.
TrialSite News has written about past challenges—see here.
An American biopharmaceutical company founded in 1990 in the Bay Area, is a research-based development stage venture that discovers and develops innovative medicines of high unmet medical need. Their R&D pipeline of new investigational drugs includes treatments for cancer, auto-immune disease and chronic pain. They develop candidates applying their proprietary PEGylation and advanced polymer conjugate technologies to modify chemical structure of substances. The company developed the world’s first inhalable non-injectable insulin, Exubera, which was awarded as the bronze award by the Wall Street Journal for its technological breakthrough. Publicly traded at $19.86 per share and a market capitalization of nearly $3.5 billion, revenues total $120 million and losses about $418 million; they do possess $1.5 billion cash. They employ between 500 to 1,000.
Lead Research/Investigator CTCA
Maurie Markman, MD, President of CTCA Medicine & Science
Alan Tan, MD, Clinical Research Medical Director, Hematologist and Medical Oncologist, CTCA Phoenix