CURE's Clinical Trial Corner: January 2020

As the cancer treatment landscape continues to grow, patients and their caregivers should be aware of the various clinical trials currently being conducted — and ones they can possibly join.

Hematologic Malignancies

Notable Labs is currently enrolling patients in its new observational clinical trial, ANSWer. The trial will take place at multiple sites across the country and will focus on blood cancers, such as acute myelogenous leukemia; multiple myeloma; myelodysplastic syndromes; lymphomas (mantle cell lymphoma); acute lymphoblastic leukemia; chronic myelogenous leukemia; and myeloproliferative neoplasms.

The study is aimed at establishing a tumor registry with annotated clinical outcomes, while exploratory assessments include correlation of ex vivo functional testing results with clinical outcomes, as well as identification of potential biomarkers that correlate clinical responses with genotype and/or phenotype.

“The observational clinical trial that we’re kicking off will give us the opportunity to test more patients than ever before, allowing us to continue increasing the platform’s predictive value,” Matt De Silva, Notable’s founder and CEO, said in a press release. “Notable’s platform improves with every patient and the ANSWer study brings our technology one step closer to being used as a tool to help physicians and patients make complex treatment decisions in the clinic which is our ultimate goal.”

Prostate Cancer

ORIC Pharmaceuticals and Astellas Pharma Inc. announced the first patient has been dosed in the multi-center, open label, dose finding phase 1b trial of ORIC-101 in combination with Xtandi (enzalutamide) to treat patients with metastatic prostate cancer that is progressing on Xtandi.

The trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ORIC-101, an investigational glucocorticoid receptor (GR) antagonist, plus Xtandi. Once the phase 2 dose of the agent is determined, the study will enroll patients into expansion cohorts based upon GR expression using ORIC's proprietary immunohistochemistry assay.

"Despite the introduction of novel antiandrogen therapies for the treatment of prostate cancer, such as enzalutamide, the majority of responsive patients will ultimately become treatment resistant, resulting in poor prognoses for men diagnosed with this devastating condition," Dr. Pratik S. Multani, chief medical officer of ORIC Pharmaceuticals, said in a press release. "We are excited to evaluate the therapeutic potential of ORIC-101 to overcome what we believe may be a key mechanism of resistance to antiandrogen therapy."

Solid Tumors

Syros Pharmaceuticals announced the first patient was dosed in its multi-center, open-label, dose-escalation phase 1 clinical trial designed to evaluate SY-5609 in patients with advanced breast, colorectal, lung or ovarian cancer, or with solid tumors of any histology that harbor Rb pathway alterations.

SY-5609, a highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor, has previously shown anti-tumor activity in preclinical studies, as a monotherapy and in combination with Faslodex (fulvestrant) in treatment-resistant models of estrogen receptor-positive breast cancer, including those resistant to both Faslodex and a CDK4/6 inhibitor.

“SY-5609 represents a promising new approach for treating a number of cancers that have eluded treatment with other targeted approaches,” study investigator Dr. Kyriakos P. Papadopoulos, co-director of clinical research at South Texas Accelerated Research Therapeutics (START), said in a press release. “We are always looking for opportunities to accelerate the development of new treatments to improve patients’ lives and give them real hope against cancer. SY-5609 has demonstrated compelling preclinical activity in a range of cancer models, and we are excited to further investigate it in this phase 1 study.”

The trial is expected to enroll 60 patients. The primary objective of the dose escalation portion of the study is to assess the safety and tolerability of escalating doses of SY-5609, with the goal of establishing a maximum tolerated dose.

Liver Cancer

Rafael Pharmaceuticals has initiated a multicenter, randomized phase 1b/2 clinical trial of devimistat (CPI-613) in combination with gemcitabine and cisplatin in patients with locally advanced, unresectable or metastatic biliary tract cancer who have had no prior treatment.

The trial aims to identify the maximum tolerated dose of devimistat that does not cause side effects, when given in combination with gemcitabine and cisplatin. In turn, this will determine the recommended dose for the randomized phase 2 part of the trial that will determine the efficacy of devimistat in combination with gemcitabine and cisplatin, compared with the chemotherapy combination chemotherapy alone. The company will enroll an estimated 68-78 patients.

“Biliary tract cancer is a rare and aggressive cancer that affects approximately 15,000 people in the United States each year,” Sanjeev Luther, president and CEO of Rafael Pharmaceuticals, said in a press release. “Launching this trial aligns with our mission to help patients with significant unmet medical needs.”