SWCRF donations move science closer to new cancer treatments as our grantees’ work leads to hopeful clinical trials

SWCRF-funded investigations are producing trials for potential cancer therapies.

On the path to developing new, minimally toxic therapies for patients, clinical trials are a crucial benchmark. Trials not only vet the efficacy of potential new cancer drugs before receiving approval from the Food and Drug Administration (FDA) but provide critical insight to the scientific community, regardless of whether or not they have positive outcomes. In the 1990s, clinical trials confirmed the efficacy of a breakthrough differentiation therapy for acute promyelocytic leukemia developed by Dr. Samuel Waxman, founder and CEO of the Samuel Waxman Cancer Research Foundation (SWCRF), in collaboration with leading researchers from Shanghai – Prof. Zhu Chen and Prof. Zhen Yi-Wang. Today, research funded in part by the SWCRF is powering several trials with the potential to produce new treatments for people living with a range of cancers. 

Prior to being approved by the FDA, new drugs must be submitted to a series of studies from early, small-scale, Phase 1 studies to late-stage, large-scale, Phase 3 studies.  According to the FDA, Phase 1 trials typically involve between 20 and 100 healthy volunteers or people with a certain disease. The study lasts for several months and determines the safety of the drug and its recommended dosage. About 70 percent of drugs studied in Phase 1 trials move on to Phase 2 studies. 

In Phase 2, up to several hundred patients are studied for up to two years to determine the drug’s efficacy and side effects. Thirty-three percent of new drugs progress to the next phase of the clinical trial process.  Phase 3 trials study between 300 and 3,000 patients for a period of up to four years to further determine a drug’s efficacy and to monitor adverse reactions. Only 25 percent to 30 percent of drugs progress from Phase 3 to the final phase, which studies the drug’s effects on thousands of patients to determine its safety.

John Crispino, PhD

SWCRF grantees have several trials in play in a range of stages, reflecting the quality – and impact -- of the research SWCRF donors are backing. “Our funded researchers are highly active in driving important trials for minimally toxic drugs in many cancers,” said Dr. Waxman. “We are most proud to support science that is moving the field closer to the goal of making cancer a chronic disease that can be managed with innovative treatments.” 

 At Northwestern University, research by SWCRF grantee John D. Crispino, Ph.D., laid the groundwork for a Phase 1 clinical study of the Aurora A kinase inhibitor Alisertib in patients with either acute megakaryoblastic leukemia or primary myelofibrosis. The trial, which launched in October of 2015, seeks to accrue 24 patients over a two-year period. The trial will expand in the coming months to include patients at the University of Miami Cancer Center and the Mayo Clinic. 

Josep M. Llovet, MD

SWCRF-funded researcher Josep M. Llovet, M.D., director of the liver cancer program at the Icahn School of Medicine at Mount Sinai, is overseeing two ongoing trials for potential treatments of two forms of liver cancer. Collaborating with Novartis, Dr. Llovet is conducting a Phase 2 study for BGJ398, an inhibitor of mutations in fibroblast growth factor receptors (FGFR), as a treatment for cholangiocarcinoma, a rare and aggressive cancer also known as bile duct cancer. The trial expects approximately 80 participants.  Dr. Llovet is also studying BLU-5454, another FGFR4 inhibitor, in partnership with Blueprint Medicines, in ongoing Phase 1 and Phase 2 studies involving patients with overexpression of FGF19, a protein that functions as a hormone that regulates bile acid synthesis.  

Drs. Robert Casero, Cynthia Zahnow and Stephen Baylin

At Johns Hopkins University, SWCRF grantees Stephen Baylin, M.D., Cynthia Zahnow, Ph.D., and Robert Casero, Ph.D., are collaborating with Celgene and investigators at the UCLA Medical Center on a Phase 2 clinical trial to study immune checkpoint inhibition in women with relapsed high-grade ovarian cancer. Pending the results of a Phase 1 trial scheduled for this summer to determine optimal dosage of oral Azacytidine (AZA), the trial will involve a randomized placebo controlled study of the anti-PD1 antibody and AZA, which blocks DNA methylation and induces an anti-viral, immune mediated tumor response. The Johns Hopkins team is also conducting a Phase 2 trial testing the effects of the anti-PD1 antibody or anti-PD1 with the HDAC inhibitor Entinostat and AZA in patients with advanced lung cancer. Results are pending.


Shai Izraeli, MD

In the area of pediatric cancer, research published by longtime SWCRF collaborator Shai Izraeli, M.D., of the Sheba Medical Center at Tel Aviv University, has led to the opening of a Phase 2 trial conducted by The Children’s Hospital of Philadelphia with the NCI’s Children’s Oncology Group to determine the impact of the JAK inhibitor Ruxolitinib combined with chemotherapy to treat a chemotherapy-resistant subtype of acute lymphoblastic leukemia (ALL). The trial protocol is awaiting final revisions pending comments from the FDA.  Given positive results, the trial, co-sponsored by Incyte Pharmaceuticals and Novartis, will expand to more sites. 



Doris Germain PhD

At Mount Sinai, SWCRF-funded breast cancer investigator Doris Germain, Ph.D., is launching a clinical trial to study fulvestrant, an anti-estrogen drug used to treat estrogen-responsive breast cancer in post-menopausal women, as a therapeutic agent for younger women with estrogen receptor positive breast cancers who typically are treated with tamoxifen. Research by Dr. Germain and Dr. Waxman showed that the biomarker cyclin D1 is indicative of resistance to tamoxifen but sensitivity to fulvestrant.  In the trial, pre-menopausal, estrogen receptor positive breast cancer patients who are also positive for cyclin D1 will be treated with either tamoxifen or fulvestrant for two to three weeks prior to their surgery to determine whether their tumors respond better to fulvestrant. 

Last year, Drs. Germain and Waxman completed a five-year Phase 2 trial testing the combination of fulvestrant and bortezomib, a drug used to treat certain blood malignancies, as a therapy for women with metastatic breast cancer who had recurred on prior anti-estrogen therapy. Patients enrolled in the trial were randomized to receive either fulvestrant alone or fulvestrant and bortezomib. The results among 118 patients tested showed that adding bortezomib to fulvestrant doubles the number of patients that had not progressed after one year compared to the group receiving fulvestrant alone. Therefore, the results suggest that adding bortezomib to fulvestrant delays progression in this heavily pretreated patient population.

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