Zotatifin Continues to Demonstrate Favorable Activity in Lung and Breast Cancer Subtypes

Treatment with zotatifin continues to appear favorable in a small population of patients with estrogen receptor (ER)–positive breast cancer and KRAS-mutant non–small cell lung cancer (NSCLC), according to a press release from eFFECTOR Therapeutics.

Investigators reported that of 7 patients who were treated with zotatifin, fulvestrant, and abemaciclib, 2 achieved confirmed partial responses and 1 experienced stable disease as of the program update in December 2022. The overall response rate was 29% and the clinical benefit rate was 43%.

The triplet regimen appeared to be safe and well tolerated. Additional ORR and CBR data will read out in the first half of 2023 for 11 other patients who are being treated.

“With zotatifin, we continue to see activity across both [ER-positive breast cancer] expansion cohorts, and the drug continues to be generally well-tolerated,” Steve Worland, PhD, president and CEO of eFFECTOR, said in the release. “The safety results to date have led us to believe that we may be able to increase the dose of zotatifin, which may achieve greater anti-tumor activity. Therefore, we have resumed dose escalation and plan to wait for dose escalation data as well as data from the ongoing [zotatifin, fulvestrant and abemaciclib] cohort before pursuing additional expansion cohorts”

Zotatifin is a potent and sequence-selective elF4A small molecule inhibitor that suppresses cancer driving protein expression. This includes Cyclins D/E, CDK2/4/6, and select RTKs and KRAS.

Zotatifin is being evaluated as part of a phase 1/2 study that includes 37 patients with advanced solid malignancies in the phase 1 portion and 18 patients in the expansion portion, which assessed the efficacy of zotatifin and fulvestrant in patients who had progressed on a CDK inhibitor. Enrollment in the triplet cohort is ongoing.

The study’s primary end points in the first potion of the study are safety and tolerability for single-agent zotatifin, recommended phase 2 dose, and pharmacokinetic profile. Moreover, end points in the second part included preliminary antitumor activity for both the single agent and combination therapy.

Moreover, in a cohort that was treated with zotatifin and fulvestrant (n = 18), a single patient had a confirmed partial response with 1 report of stable disease exceeding 24 weeks. Safety was similarly positive for the doublet regimen.

Investigators observed dose dependent target engagement via 2 methods and did not observe obvious target saturation, prompting the dose escalation trial to resume.

Initiation has been deferred for a cohort of patients with cyclin D1–amplified ER-positive breast cancer and enrollment paused for a group with KRAS G12C–mutant lung cancer until dose escalation concludes.

Reference

eFFECTOR Therapeutics provides positive clinical data update for zotatifin and general corporate update. News release. eFFECTOR Therapeutics. January 5, 2023. Accessed January 9, 2023. https://bit.ly/3k2aWjw