Cyteir Therapeutics Announces Presentation of First-in-Human Phase 1/2 Study of CYT-0851
- Category: Small Molecules
- Published on Saturday, 05 June 2021 12:38
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- Phase 1 interim analysis data presented at oral session at the annual meeting of the American Society of Clinical Oncology (ASCO)
- Treatment-related adverse events occurred infrequently and were low-grade and manageable
- Responses during dose-escalation have been observed in patients with DLBCL, follicular lymphoma and soft tissue sarcoma
LEXINGTON, MA, USA I June 4, 2021 I Cyteir Therapeutics, a leader in the discovery and development of next-generation synthetically lethal therapies for cancer, today announced the presentation of an interim analysis of the Phase 1 portion of a first-in-human Phase 1/2 study of CYT-0851. CYT-0851 is an oral, small molecule inhibitor of RAD51-mediated homologous recombination. The presentation was given at an oral session of the 2021 American Society of Clinical Oncology (ASCO) meeting.
The Phase 1 portion of the trial began enrolling patients with advanced hematologic cancers and solid tumors in September 2019. Patients were treated with continuous 28-day cycles of increasing oral doses of CYT-0851. The primary objective of the ongoing Phase 1 study is to identify the maximum tolerated dose (MTD). The key secondary objectives are evaluation of the safety, pharmacokinetics, and preliminary anti-tumor activity.
As of the April 6, 2021 data cutoff, 35 patients were treated with CYT-0851 across eight dose-escalation cohorts. Thirty-five patients were evaluable for safety and 21 patients were evaluable for efficacy. Patients had a median of four prior lines of therapy. Twenty-three patients discontinued treatment due to progressive disease (19), patient decision (2), physician decision (1) or adverse event (1). The adverse event that led to discontinuation was an increase in the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) that was secondary to the patient's cancer.
To date, CYT-0851 has been well-tolerated with 63% of patients reporting no treatment related adverse events. Thirteen patients (37.1%) experienced treatment-related adverse events with most events being low-grade. There have been no reported treatment-related Grade 4 or 5 events. The most common treatment-related adverse events were an increase in blood alkaline phosphatase levels (8.6%), fatigue (8.6%) and nausea (8.6%). There have been no reported dose-limiting toxicities, clinically significant myelosuppression, treatment discontinuations due to treatment-related adverse events, or treatment-related serious adverse events.
At the time of the data cutoff, there were 21 patients who were response evaluable. Three partial responses were observed in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and soft tissue sarcoma. The patients with DLBCL and FL had confirmed responses according to Lugano criteria and the patient with sarcoma had a response that was unconfirmed according to RECIST. Ten patients had a best response of stable disease and four patients have been on therapy for more than six months, including the three patients that responded to treatment.
The study continues to dose-escalate to identify the MTD and enrollment is ongoing in the 400mg once daily dose cohort. Upon identification of the MTD, a Phase 2 dose will be selected, and the Phase 2 expansion cohorts are expected to begin enrollment in the second half of 2021.
About Cyteir Therapeutics
Cyteir Therapeutics is a clinical-stage oncology company that is focused on the discovery and development of next-generation synthetically lethal therapies to treat cancer. The company is using its expertise in DNA damage response (DDR) biology to advance a pipeline of novel drug candidates that selectively target key cancer vulnerabilities. Cyteir's wholly owned lead compound, CYT-0851, is a potent and selective, oral investigational drug that was designed to inhibit RAD51-mediated homologous recombination (HR) and the repair of double-strand DNA (dsDNA) breaks. For more information, visit www.cyteir.com.
SOURCE: Cyteir Therapeutics