First-in-Human Clinical Trial of ONC201 in Patients With Refractory Solid Tumors

Key Points

  • While the study achieved the aim of identifying the recommended phase II dose of the drug, findings also showed tumor regression in patients with metastatic disease.
  • Results demonstrated prolonged stable disease following more than 9 cycles (27 weeks) of treatment—particularly in patients with prostate and endometrial cancer that had lymph node, bone, and lung lesion involvement.
  • Of the 28 participants, 10 completed at least 4 cycles of treatment, with 2 patients receiving at least 9 cycles. There were no drug-related adverse events worse than grade 1 in either the dose-escalation phase or the expansion phase.

A first-in-human clinical trial examining the investigational small-molecule drug ONC201 in patients with advanced solid tumors showed the oral agent to be well tolerated at the recommended phase II dose, according to Rutgers Cancer Institute of New Jersey investigators whose research also showed early signs of clinical benefit in patients with advanced prostate and endometrial cancers. The work was published by Stein et al in Clinical Cancer Research.

The first of a new family of therapeutic compounds called imipridones, ONC201 targets a dopamine receptor that is a member of the G protein–coupled receptor superfamily residing on the surface of cancer cells. Previous research on the study drug conducted by Rutgers Cancer Institute and Oncoceutics, Inc—which is also supporting this trial—suggested that ONC201 may be capable of turning off proteins that maintain tumor growth and and may help kill cancer cells while sparing normal ones. Preclinical study demonstrated ONC201 was effective in laboratory models against a number of solid tumors including colon cancer, brain cancer, triple-negative breast cancer, and non–small cell lung cancer.

Study Findings

In this phase I dose-escalation study, 10 patients over age 18 with advanced solid tumors that were resistant to standard therapies were enrolled through Rutgers Cancer Institute between January 2015 and July 2015. Participants received a starting dose of 125 mg of the study drug, which was taken orally via capsule every 21 days (1 cycle). The dosage for this cohort was increased incrementally up to a maximum dose of 625 mg, which is fivefold above the dose that was effective in laboratory models. An additional 18 patients were enrolled in an expansion phase between August 2015 and February 2016 and treated at the recommended phase II dose of 625 mg in order to collect additional safety, pharmacokinetic, and pharmacodynamic information.

While the study achieved the aim of identifying the recommended phase II dose of the drug, findings also showed tumor regression in patients with metastatic disease. Results demonstrated prolonged stable disease following more than 9 cycles (27 weeks) of treatment—particularly in patients with prostate and endometrial cancer that had lymph node, bone, and lung lesion involvement. Of the 28 participants, 10 completed at least 4 cycles of treatment, with 2 patients receiving at least 9 cycles. The authors noted that while a 90-year-old prostate cancer patient saw his primary tumor and metastatic bone lesion shrink by about 25% after taking two 625-mg doses of ONC201, a 72-year old patient with advanced clear cell endometrial cancer had a mixed response after two doses, with multiple nodes decreasing by more than 30% but experiencing the development of new nodes.

There were no drug-related adverse events worse than grade 1 in either the dose-escalation phase or the expansion phase. The few low-grade events that were recorded (nausea, fever) were resolved quickly, noted the authors.

“By exploring a novel agent that targets the cancer but leaves noncancerous tissue untouched, we have an opportunity to not only provide a new treatment option for patients who have exhausted standard forms of therapy without the typical toxicities associated with anticancer treatment, but to also offer them a therapeutic that may result in a better quality of life since healthy cells are not impacted,” noted Rutgers Cancer Institute medical oncologist Mark Stein, MD, Associate Professor of Medicine at Rutgers Robert Wood Johnson Medical School and lead investigator of the work. “While meaningful to confirm the safety profile of this dosage for ONC201, it is noteworthy that our findings also showed some evidence of clinical benefit to some patients.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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