On May 25, 2023, eFFECTOR Therapeutics, Inc. announced positive interim data updates from a Phase 2 expansion cohort evaluating zotatifin combined with fulvestrant and abemaciclib in patients with ER+ metastatic breast cancer (“mBC”). These data, as well as initial data from further dose escalation, will be presented as part of a poster presentation at the American Society of Clinical Oncology Annual Meeting in Chicago, Illinois. New interim data were presented on the fully enrolled expansion cohort of patients (n=20) who received the ZFA triplet with zotatifin dosed at 0.07 mg/kg on Days 1 and 8 of 21-day cycles.

Patients were heavily pre-treated, having received a median of four prior lines of therapy for metastatic disease. Five out of 19 (26%) RECIST-evaluable patients achieved a partial response (“PR”), including four confirmed and one unconfirmed. All five patients who achieved a PR had previously progressed on prior CDK4/6 and fulvestrant treatments, and all 5 had received one or more prior lines of chemotherapy.

The disease control rate (“DCR”), reflecting patients with at least one on-treatment scan showing PR or stable disease (“SD”), was 14 of 19 (74%). PRs were seen in patients with and without mutations in the ESR1 and PIK3CA genes. As of the data cutoff date, 4 patients remained on therapy and progression free survival (“PFS”) as well as clinical benefit rate (“CBR”) data are not yet mature.

The ZFA triplet was generally well tolerated, with 3 patients discontinuing due to adverse events (“AEs”) of any cause, and the large majority of AEs being Grade 1 or 2. The most frequent Grade 3 AEs were diarrhea in 3 of 20 (15%) patients, similar to the 13% frequency reported in the registrational Monarch 2 trial for abemaciclib and fulvestrant, and dyspnea in 2 of 20 (10%) patients. New data were also reported for patients in resumed dose escalation cohorts utilizing zotatifin combined with fulvestrant (“ZF doublet”). In the one fully enrolled cohort, wherein patients received zotatifin dosed at 0.1 mg/kg every other week (“Q2W”) combined with fulvestrant, 1 of 3 (33%) patients achieved a PR on the first on-treatment scan, which was confirmed on the second on-treatment scan that occurred after the data cutoff, and remained on study.

This patient had received four lines of prior therapy for metastatic disease, with progressive disease (“PD”) being the best overall response (“BOR”) to all four prior lines. Dose escalation is continuing at 0.14 mg/kg Q2W and 0.07 mg/kg once weekly (“QW”). Zotatifin has been generally well tolerated in dose escalation cohorts, with no dose limiting toxicities or serious adverse events observed.