CYT-0851 Plus Capecitabine Demonstrates Efficacy in Advanced Ovarian Cancer

Markus Renschler, MD

The combination of the novel MCT inhibitor CYT-0851 and capecitabine (Xeloda) displayed clinical activity and a tolerable safety profile in patients with advanced platinum-resistant ovarian cancer, according to findings from a dose-expansion cohort of a phase 1/2 trial (NCT03997968) presented during the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.¹

At the September 26, 2023, data cutoff, efficacy-evaluable patients with advanced ovarian cancer (n = 11) experienced a disease control rate (DCR) of 91% and a median progression-free survival of 170 days. Confirmed partial responses (PRs) per RECIST were observed in 2 patients, 1 experienced an unconfirmed PR, 7 had stable disease (SD), and 1 had progressive disease (PD).

Patients had a median of 6 prior lines of therapy. Most patients were platinum-resistant (n = 7) and 4 were platinum-refractory. Nearly all patients (n = 10) received CYT-0851 at the recommended phase 2 dose (RP2D) of 400 mg daily and 1 patient was treated with CYT-0851 at a dose of 300 mg daily.

In terms of safety, no unexpected adverse effects (AEs) were reported at clinically active doses, and there were no treatment discontinuations or reductions due to treatment-related adverse effects (TRAEs). All TRAEs were of grade 1 to 2 severity; commonly occurring AEs included fatigue (46%), decreased appetite (18%), diarrhea (18%), nausea (18%), palmar-plantar erythrodysesthesia syndrome (18%), and vomiting (18%).

“The results from the expansion cohort support the initial findings in our phase 1 dose-escalation study of CYT-0851 in combination with capecitabine in ovarian cancer, confirming a high level of tumor control with an all-oral outpatient regimen that was generally well tolerated,” Markus Renschler, MD, president and chief executive officer of Cyteir, the manufacturer of CYT-0851, said in a news release.²

The phase 1/2 study enrolled patients with advanced ovarian, breast, and pancreatic cancer as well as those with soft tissue sarcoma and head and neck squamous cell carcinoma, and an ECOG performance status of 1 or less. Patients were treated with oral CYT-0851 in a 3 + 3 dose-escalation design, with a starting dose of 100 mg and a maximum dose of 400 mg given daily. CYT-0851 was given in combination with oral capecitabine at a dose of 1000 mg/m2 twice daily on days 1 to 14 of each 21-day cycle or intravenous gemcitabine administered at a dose of 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Treatment continued until PD, unacceptable toxicity, or patient withdrawal.²

The primary end point was determining the RP2D and the maximum-tolerated dose of CYT-0851 in combination with capecitabine and gemcitabine. Secondary end points included safety and tolerability, preliminary antitumor activity, and pharmacokinetics.

Previous findings presented at the 2023 ASCO Annual Meeting showed that at a data cutoff of May 1, 2023, efficacy-evaluable patients who received CYT-0851 plus capecitabine at any dose level (n = 14) achieved a DCR of 71.4%, with 9 patients experiencing SD and 1 confirmed PR in a patient with ovarian cancer.

In the safety population (n = 22), 45.5% of patients who received CYT-0851 in combination with capecitabine experienced any-grade AEs and 9.1% had grade 3 or 4 AEs. The most common any-grade TRAEs included fatigue (27.3%), decreased appetite (13.6%), and nausea (13.6%).

References

1. Ongoing results from a dose expansion cohort of CYT-0851 in combination with capecitabine in advanced platinum-resistant ovarian cancer show promising clinical activity and generally well tolerated safety profile. News release. Cyteir Therapeutics, Inc. October 12, 2023. Accessed October 12, 2023. https://www.businesswire.com/news/home/20231012887827/en/
2. Lynch RC, Munster PN, Falchook GS, et al. Phase 1 results of CYT-0851, a monocarboxylate transporter (MCT) inhibitor, in combination with capecitabine (cape) or gemcitabine (gem) in advanced solid tumors. J Clin Oncol. 2023;41(suppl 16):3099. doi:10.1200/JCO.2023.41.16_suppl.3099