Study title: A study of imlunestrant versus standard endocrine therapy in participants with early breast cancer (EMBER-4)

Summary: Breast cancer is commonly diagnosed worldwide, often at an early stage. Endocrine therapy given for 5- to 10-years, has been the standard of care adjuvant treatment for patients with early breast cancer that is estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-). Unfortunately, a meaningful proportion of women initially diagnosed with early breast cancer that is ER+, HER2- eventually experience disease relapse despite receiving the standard of care adjuvant treatment.

This study evaluates imlunestrant, an investigational oral estrogen receptor degrader, versus standard hormone therapy for those with early ER+, HER2- breast cancer who have undergone 2 to 5 years of endocrine therapy and are at higher risk of recurrence. Kaiser Permanente Southern California is among the highest accruing sites for its objective, according to the trial sponsor. See NCT05514054 for more information.

Principal investigator: Sujatha Murali, MD, MS

Locations: San Marcos, Zion, Fontana, Ontario, Riverside, Los Angeles, Baldwin Park, Panorama City, Woodland Hills, South Bay, West Los Angeles, Bellflower, Anaheim, and Irvine

Study title: Five or ten year colonoscopy for 1-2 non-advanced adenomatous polyps (FORTE)

Summary: Colonoscopy can detect and prevent colorectal cancer by allowing doctors to identify and remove adenomas. After adenomas have been detected, patients are typically advised to return for surveillance colonoscopy. Current guidelines recommend that patients with 1 or 2 adenomas that are not advanced return in 5 to 10 years for follow-up surveillance colonoscopies. However, there remains a lack of clear guidance on determining which individuals should be triaged for follow-up at 5 years versus 10 years.

This study aims to assess the benefits of surveillance colonoscopy in patients with non-advanced adenomas. It will evaluate the incidence of colorectal cancer among participants with 1 to 2 non-advanced adenomas who are randomized to undergo surveillance colonoscopy at 10 years, in comparison to those randomized to surveillance colonoscopy at both 5 and 10 years. The findings will influence decisions on the frequency of colonoscopy procedures, which affect large portions of the population.

See NCT05080673 for more information.

Principal investigator: Ahmed Megahed, MD

Locations: San Marcos, Zion, Fontana, Ontario, Riverside, Los Angeles, Baldwin Park, Panorama City, Woodland Hills, South Bay, West Los Angeles, Bellflower, Anaheim, and Irvine

Study title: A study of dostarlimab in untreated dMMR/MSI-H locally advanced rectal cancer

Summary: This study investigates dostarlimab monotherapy for locally advanced mismatch-repair deficient (dMMR) rectal cancer without prior treatment. Approximately 5 to 10% of rectal cancers are dMMR

Participants who achieve complete clinical response following dostarlimab treatment will undergo non-operative management, including close surveillance for recurrent disease. The goal is to see if dostarlimab therapy alone can help avoid chemotherapy, radiation, and surgery. See NCT05723562 for more information.

Principal investigator: Gary Buchschacher Jr., MD, PhD

Locations: San Marcos, Zion, Fontana, Ontario, Riverside, Los Angeles, Baldwin Park, Panorama City, Woodland Hills, South Bay, West Los Angeles, Bellflower, Anaheim, and Irvine

Study title: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US)

Summary: No biomarkers have yet been validated prospectively in randomized studies for resected colon cancer to determine the need for adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) in the bloodstream is a specific and sensitive approach for identifying microscopic or residual tumor cells in colon cancer patients, especially with serial monitoring. It may be more effective than traditional clinical and pathological features in predicting recurrence risk.

Patients without detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may not need adjuvant chemotherapy. Furthermore, the optimal adjuvant chemotherapy regimen with detectable ctDNA, who are at high risk for recurrence, has not been established.

This trial will evaluate chemotherapy recommendations based on ctDNA presence after colon cancer surgery. See NCT05174169 for more information.

Principal investigator: Gary Buchschacher Jr., MD, PhD

Locations: San Marcos, Zion, Fontana, Ontario, Riverside, Los Angeles, Baldwin Park, Panorama City, Woodland Hills, South Bay, West Los Angeles, Bellflower, Anaheim, and Irvine

Study title: Comparing cisplatin every three weeks to cisplatin weekly when combined with radiation for patients with advanced head and neck cancer

Summary: This trial evaluates high-dose cisplatin every three weeks combined with radiation therapy against low-dose weekly cisplatin with radiation therapy in treating locoregionally advanced head and neck cancer. Chemotherapy drugs like cisplatin halt tumor growth by killing cells, preventing division, or stopping spread. Radiation therapy uses high-energy x-rays to kill tumor cells and reduce tumors.    This study aims to determine if low-dose cisplatin given weekly together with radiation therapy is the same or better than high-dose cisplatin given every 3 weeks together with radiation therapy in treating patients with head and neck cancer. For more information see NCT05050162.

Principal investigator: Gary Buchschacher Jr., MD, PhD

Locations: Los Angeles, Anaheim, Irvine, Ontario, and Bellflower

Study title: A study to investigate blinatumomab in combination with chemotherapy in patients with newly diagnosed B-lymphoblastic leukemia (B-ALL)

Summary: This trial assessed the addition of blinatumomab, an immune-based therapy, to standard chemotherapy for newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) in children. Blinatumomab binds to cancer cells and T-cells, using the patient’s immune system to attack the cancer.

The study’s primary objective was to see if the addition of 2 cycles of blinatumomab to standard chemotherapy would improve outcomes for patients with newly diagnosed B-ALL of average or higher risk.

Results of the study, published in The New England Journal of Medicine, showed significant improvement in disease-free survival, leading to changes in childhood leukemia treatment. For more information see NCT03914625.

Principal investigator: Robert Cooper, MD

Location: Los Angeles

Study title: Testing MK-3475 (pembrolizumab) after surgery for localized muscle-invasive bladder cancer and locally advanced urothelial cancer (AMBASSADOR)

Summary: This study evaluated the use of pembrolizumab, an immunotherapy, as an additional treatment after surgery for bladder cancer that has spread deep into the muscle of the bladder wall or urothelial cancer that has spread from its origin to nearby tissue or lymph nodes. Pembrolizumab is an immune checkpoint inhibitor that targets the protein PD-1 on immune cells to help them recognize and attack cancer cells. It is approved to treat various cancers, often in combination with other therapies.

The study found that disease-free survival was significantly longer among patients with high-risk muscle-invasive urothelial carcinoma who received adjuvant pembrolizumab after surgery.

Findings were published in The New England Journal of Medicine. For more information, see NCT03244384.

Principal investigator: Helen Moon, MD

Locations: Bellflower, Fontana, Anaheim, Irvine, Panorama City, San Marcos, West Los Angeles, and Woodland Hills

Study title: Mirvetuximab soravtansine with bevacizumab versus bevacizumab as maintenance in platinum-sensitive ovarian, fallopian tube, or peritoneal cancer (GLORIOSA)

Summary: This high-priority trial evaluates the use of mirvetuximab soratansine with bevacizumab for maintenance therapy for FRα-high, recurrent platinum-sensitive ovarian cancer. Mirvetuximab soratavansine, also known as MIRV, is an antibody-drug conjugate. It is the first and only drug to have received FDA approval for treatment of recurrent ovarian cancer and is now being investigated for different indications.

The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRα). Patients must have confirmation of FRα positivity. For more information, see NCT05445778

Principal investigator: Devansu Tewari, MD, MBA

Location: Orange County

Study title: Standard chemotherapy versus chemotherapy guided by cancer stem cell test in recurrent glioblastoma.

Summary: This study evaluated whether a second tumor resection and chemotherapy, guided by a proprietary in vitro chemosensitivity assay, would improve survival over physician-choice chemotherapy in recurrent glioblastoma.

Results published in Cell Reports Medicine showed the ChemoID assay group had a median overall survival of 12 months, 4.5 months longer than the 7.5 months with physician-choice. Out of nearly 80 participants, 15 were Kaiser Permanente members, including 10 in the assay group. For more information, see NCT03632135.

Principal investigator: Richard Green, MD

Location: Los Angeles

Study title: Ramucirumab plus pembrolizumab versus usual care for treatment of stage IV or recurrent non-small cell lung cancer following immunotherapy (PRAGMATICA-LUNG).

Summary: This study compares the effectiveness of the combination of ramucirumab and pembrolizumab to the standard of care for treatment of non-small cell lung cancer that is stage IV or has recurred. Ramucirumab is a monoclonal antibody that may stop the growth of new blood vessels that tumors need to progress.

The study has a novel design that seeks to prioritize patient access, removing eligibility barriers so that participants are treated based on clinical standards while collecting only necessary data and maintaining safety. This approach could lead to more inclusive, lower cost studies that could reach broader populations of patients. For more information, see NCT05633602.

Principal investigator: Eric McGary, MD, PHD, MPH

Location: Los Angeles

Study title: A interventional, phase 1b, randomized, double-blind, sponsor open, placebo-controlled, multi-center, dose-finding study to evaluate safety, tolerability and pharmacokinetics of sisunatovir in pediatric participants up to age 60 months with respiratory syncytial virus (RSV) lower respiratory tract infection

Summary: This randomized, placebo-controlled study looks at the efficacy and safety of sisunatovir in pediatric patients with RSV (respiratory syncytial virus) lower respiratory tract infections. There are currently limited treatment options available for RSV, a disease that leads to the death of over 100,000 children a year worldwide.

The first patient enrolled in this trial was at Kaiser Permanente in Los Angeles. At the time, no other treatment was available for pediatric patients with RSV. For more information, see NCT06102174.

Principal investigator: William Towner, MD

Location: Los Angeles

Study title: A randomized, double blind, placebo-controlled study of LMN-201 for prevention of C. difficile infection recurrence (RePreve)

Summary: This study aims to evaluate the safety, tolerability, and effectiveness of LMN-201 combined with standard antibiotics to prevent C. difficile infection (CDI) recurrence.

The trial uses a multi-phase approach. Part A is an open-label phase where participants receive LMN-201 with standard of care antibiotics for 7 days, followed by a 4-week observation phase and a 22-week follow-up phase for safety monitoring. The sentinel safety data will be reviewed before expanding into part B, which will be open to participants with CDI and a positive stool toxin B immunoassay collected no more than 7 days before the study drug is administered.

Kaiser Permanente Southern California is a top enroller in the United States with the most diverse population in age and race. Participants have been enrolled from across the region. For more information, see NCT05330182.

Principal investigator: William Towner, MD

Location: Los Angeles

Study title: A study of LBP-EC01 in the treatment of acute uncomplicated UTI caused by drug resistant E. coli (ELIMINATE Trial)

Summary: The evaluates a novel treatment for urinary tract infections using a blend of bacteriophages and CRISPR technology to target E. coli, the primary cause of urinary tract infections, or UTIs. This dual mechanism of action not only destroys E. coli but also enhances the efficacy of existing antibiotics against both non-drug resistant and drug-resistant strains.

By potentially improving patient outcomes and reducing antibiotic resistance, this treatment addresses a critical unmet need in treating recurrent UTIs, especially those caused by multi-drug resistant strains. For more information, see NCT05488340.

Principal investigator: Jonathan (Hien) Truong, MD

Location: Antelope Valley

Study title: rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial

This study seeks to establish the first treatment for acute spontaneous intracerebral hemorrhage within a time window and subgroup of patients that is most likely to benefit. The central hypothesis is that drug recombinant Factor Vlla (rFVIIa), administered within 120 minutes from stroke onset with an identified subgroup of patients most likely to benefit, will improve outcomes at 180 days as measured by the Modified Rankin and decrease ongoing bleeding as compared to standard therapy.

Kaiser Permanente Southern California is 1 of only 2 systems in the country utilizing telemedicine for enrollment at a primary stroke center. It has been recognized as the second highest-ranked enrolling system in the FASTEST trial. For more information, see NCT03496883.

Principal investigator: Navdeep Sangha, MD

Location: Los Angeles

Study title: Determinants of incident stroke cognitive outcomes and vascular effects on recovery (Discovery)

Summary: This study examines factors influencing post-stroke cognitive outcomes, including vascular risks, pre-existing conditions, stroke lesion locations, and genetic variations. It aims to uncover mechanisms affecting recovery and dementia risks.

The prospective, multicenter study involves 8,000 acute stroke participants enrolled within six weeks of onset. It includes baseline screenings, follow-ups, cognitive tests, blood draws, and advanced imaging like MRIs and PET scans.

By focusing on diverse populations, this research seeks to improve personalized interventions for stroke recovery. In 2024, Kaiser Permanente Southern California stood out as a top-enrolling site, emphasizing Hispanic and Asian inclusion. For more information, see the Discovery study website.

Principal investigator: Navdeep Sangha, MD

Location: Los Angeles

Study title: AMPLATZER PFO Occluder Post Approval Study (PFO PAS)

Summary: This post-approval study seeks to assess the safety and effectiveness of 2 cardiac device systems, the Amplatzer Talisman™ PFO Occlusion System and the Amplatzer PFO Occluder. The device systems are designed to treat people with patent foramen ovale (PFO) — a hole in the heart that doesn’t seal after birth — who have had a stroke and are at risk of another. Untreated persistent PFO can lead to stroke. Understanding the safety and effectiveness of this minimally invasive device could potentially improve patient outcomes.

The Los Angeles Medical Center Cardiac team was recognized as the top enrolling site study-wide. For more information about the study, see NCT03309332.

Principal investigator: Somjot Brar, MD, MPH

Location: Los Angeles

Study title: ENVISION IDE trial: Safety and effectiveness of Navitor in transcatheter aortic valve implantation (ENVISION)

This study is evaluating the use of the Navitor TAVI System in patients with symptomatic, severe aortic stenosis who are at intermediate or low surgical risk. Results of this trial may expand availability of this device to a new group of patients who are candidates for TAVI and help future patients with similar health conditions receive optimal treatment.

The study, which is being conducted at 95 sites globally, is the first clinical trial at the Fontana Medical Center Catheter lab. For more information about the study, see NCT05932615.

Principal investigator: William Mosley, MD

Location: Fontana

Study title: Study of ravulizumab in immunoglobulin A nephropathy (IgAN) (ICAN)

Summary: This study is exploring a treatment for Immunoglobulin A nephropathy (IgAN) which can lead to kidney failure in up to 30% of patients within 20 years.  This is a condition without a cure and requires multiple medications and supportive care to manage symptoms, but studies such as this offer a way to better understand and treat this disease.

The primary objective of this study to evaluate efficacy of ravulizumab compared with placebo on proteinuria reduction and change in eGFR in adult participants with IgAN who are at risk of disease progression. For more information about the study, see NCT06291376.

See related story on Dr. Sim’s research on incidence of IgAN nephropathy here.

Principal investigator: John Sim, MD

Location: Los Angeles

Study title: A community-based, pop-up clinical study exploring genetic and environmental determinants of ALS in underrepresented ethnic groups (TALS-002)

Summary: Although ALS exists in people of all ancestries, participants in prior ALS research studies and clinical trials were more than 90% Caucasian. This study seeks to expand inclusion of historically underrepresented ethnicities and races, which is a missing yet critical part of understanding the genetic risk factors for ALS. 

The goal of the study is to collect a blood sample in approximately 6,000 diverse and underrepresented individuals living with ALS and healthy controls. Long-read Whole Genome Sequencing (WGS) will be performed on all DNA samples collected. These methods allow for high accuracy in long-read sequencing and richer data generation not easily detected using short- read sequencing methods, such as repeat expansions and epigenetic changes to DNA.

Our Rare Disease team held the first nationwide pop-up event at the Los Angeles Medical Center for this study. For more information about this study, see the Target ALS website.

Principal investigator: Abel Wu, MD

Location: Los Angeles

Study title: Pivotal 2 study of RGX-314 gene therapy in participants with nAMD (ASCENT)

Summary: Age-related macular degeneration, or AMD, is a progressive degenerative macular disease attacking the region of highest visual acuity, the macula. The neovascular or “wet” form of the disease, or nAMD, is characterized by proliferation of blood vessels and cells. Ultimately, photoreceptor death and scar formation result in a severe loss of central vision and the inability to read, write, recognize faces, or drive.

Preventive therapies for nAMD have demonstrated little effect, and therapeutic strategies have focused primarily on treating the neovascular lesion.

The long-term, stable expression of the ABBV-RGX-314 TP following a 1-time gene therapy treatment for nAMD could potentially reduce the treatment burden of currently available antiVEGF therapies while maintaining vision with a favorable benefit/risk profile. For more information on the study, see NCT05407636.

Principal investigator: Vivienne Hau, MD, PhD

Location: Riverside

Study title: A study of the safety and tolerability of ASP7317 in senior adults who are losing their clear, sharp central vision due to geographic atrophy secondary to dry age-related macular degeneration.

Summary: Age-related macular degeneration, or AMD, is an eye disease that causes people to lose their sharp central vision over time. Aging damages the macula, which is in the middle of the retina — the light-sensitive part at the back of the eye. There are 2 types of AMD: wet AMD and dry AMD. The advanced stage of dry AMD causes vision loss; this is known as geographic atrophy. AMD makes everyday tasks, like reading or driving, difficult.

ASP7317 is a potential new treatment for people with AMD. ASP7317 are human stem cells that have changed into cells found in the retina. ASP7317 is injected under the macula. It is hoped that ASP7317 will replace some of the damaged cells in the macula and improve vision for people with dry AMD. For more information on this study, see NCT03178149.

Principal investigator: Vivienne Hau, MD, PhD

Location: Riverside