On June 5, 2022 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported that results from a Phase 1 dose escalation monotherapy trial with CYT-0851 in a poster titled "Phase 1 Results of CYT-0851 in Patients with Advanced Solid and Hematologic Cancers" (Abstract: 3084, Poster: 76) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, Illinois (Press release, Cyteir Therapeutics, JUN 5, 2022, View Source [SID1234615582]).
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"Data presented today from the Phase 1 dose escalation study with CYT-0851 show that the drug has performed well in advanced, relapsed and/or refractory cancer patients: it has desirable pharmacologic properties with an estimated half-life of three days, dose proportional exposure, and a dose dependent, predictable, and favorable safety profile. In addition, anti-tumor activity was observed with disease stabilization and responses in patients with solid tumors and hematologic malignancies, supporting the advancement of CYT-0851, as a potentially first-in-class drug, into Phase 2 expansion cohorts as a monotherapy and Phase 1 in combination with standard of care treatment regimens," said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. "The Cyteir team continues to execute on the clinical development of CYT-0851 and we look forward to sharing data in the second half of 2022."
Phase 1 Dose Escalation Results
The primary objectives of the Phase 1 dose escalation trial with CYT-0851 were to determine the recommended Phase 2 dose, determine the maximum tolerated dose (MTD) and to evaluate safety and tolerability. Key secondary objectives include determination of the pharmacokinetic parameters, optimal dosing regimen and preliminary anti-tumor activity. As of the April 13, 2022 data cutoff, 80 patients were enrolled across twelve dose-escalation cohorts from 30 mg to 1200 mg total daily dose. Eighty patients were evaluable for safety and 65 patients were evaluable for efficacy.
The maximum tolerated dose was determined to be 600 mg once a day for both solid tumors and hematologic malignancies. The recommended Phase 2 dose is 400 mg once a day, a convenient and commercially attractive schedule.
Key Findings
In solid tumors:
Forty-five patients were response evaluable and one unconfirmed partial response (PR) was achieved in a patient with soft-tissue sarcoma who was treated for almost 11 months
Nineteen patients (42%) had stable disease and twelve patients (27%) had a decrease in target lesion size for an overall disease control rate of 44%
Stable disease (42%) was seen in patients with soft-tissue sarcoma, head and neck squamous cell, pancreatic, ovarian, and breast cancers
In hematologic cancers:
Eighteen patients with non-Hodgkin lymphoma were response evaluable
Responses were seen in patients with follicular lymphoma (1 complete response (CR) and 1 PR) and diffuse large B-cell lymphoma (1 PR)
Three patients with follicular lymphoma, one patient with diffuse large B-cell lymphoma and one patient with hairy-cell leukemia achieved stable disease
Patients responding to CYT-0851 exhibited a durable clinical benefit as evidenced by the more than 18 months of treatment in the patient with follicular lymphoma who achieved a CR
Safety:
To date, CYT-0851 has exhibited a generally well tolerated safety profile with 42% of patients reporting no treatment related adverse events (TRAEs)
At the recommended Phase 2 dose or below, no patient discontinued therapy for TRAEs
The most common TRAEs were fatigue (18%), alopecia (14%), nausea (11%), hyperuricemia (10%), constipation (8%) and anemia (8%)
The dose limiting toxicity was reversible metabolic acidosis, consistent with the mechanism of action of the drug
"The Phase 1 data for monotherapy CYT-0851 has demonstrated promising clinical activity with a manageable safety profile across a wide array of cancers in a heavily pretreated patient population," said Dr. Ryan C. Lynch, Assistant Professor at the Fred Hutchinson Cancer Center and first author of the study. "The broad activity coupled with the mechanistic understanding that CYT-0851 is impacting cancer cell metabolism creates a promising therapeutic approach for use in a wide range of cancers."
CYT-0851 Mechanism of Action Insights Have Potential to Expand into Additional Tumor Types
Based on new molecular, bioinformatic, and biochemical characterization research that has been done at Cyteir to elucidate the mechanism of action of CYT-0851, management believes that the observed effects of CYT-0851 on the viability of cancer cells are due to inhibition of monocarboxylate transporter (MCT) activity and the subsequent disruption of lactate transport. Monocarboxylate transporters are essential proteins in cancer metabolism making MCTs an attractive target for cancer therapy. This new understanding of the mechanism of action of CYT-0851 could potentially accelerate development of a biomarker and allow for expansion into additional opportunities in other tumor types.
Data from the Ongoing Phase 2 Monotherapy Expansion Cohorts and Phase 1 Combination Study Expected in 2H 2022
Cyteir continues to make progress advancing CYT-0851 in monotherapy and combination clinical studies. Enrollment is ongoing in six disease-specific Phase 2 expansion cohorts with monotherapy in hematologic malignancies and solid tumors. Completion of enrollment in stage 1 of this study is expected before the end of 2022. Enrollment is also ongoing in a Phase 1 combination study of CYT-0851 with three standard-of-care regimens: (1) rituximab plus bendamustine; (2) gemcitabine; and (3) capecitabine, in both hematologic malignancies and solid tumors. Initial safety data from this combination study is expected before the end of 2022.