The FDA has granted breakthrough therapy designation to TERN-701 for the treatment of Ph-positive chronic myeloid leukemia in chronic phase.
The BCR::ABL1 inhibitor TERN-701 has received breakthrough therapy designation from the FDA for the treatment of patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP-CML) who do not harbor a BCR::ABL1 T315I mutation and were treated with at least 2 previous TKIs.1
The regulatory decision was based on
“There remains an urgent need for CML treatments that offer improved efficacy, safety, and tolerability over current therapies,” Scott Harris, chief development and operations officer at Terns Pharmaceuticals, stated in a news release.1 “This designation from the FDA supports the significant potential of TERN-701 to be a best-in-disease therapy for [patients with] CML and offers substantial improvement based on the faster, deeper responses compared [with] prior TKIs and encouraging safety and tolerability profile observed to date.”
The open-label, multicenter study enrolled patients at least 18 years of age with CP-CML.2 During dose escalation, prior treatment with at least 2 TKIs or progression/suboptimal response to a frontline second-generation TKI was required; in dose expansion, treatment failure or suboptimal response to at least 1 prior TKI was required. Prior TKIs such as asciminib (Scemblix) and ponatinib (Iclusig) were permitted. Both patients with or without T315I mutations were allowed to enroll during dose escalation, whereas only patients without T315I mutations were allowed to enroll in part 2 of the study.
Patients received TERN-701 once per day for continuous 28-day cycles. Throughout the first dose escalation part of the study, TERN-701 was given at doses of 160 mg, 320 mg, 400 mg, and 500 mg. In the second part of the study, TERN-701 was given to patients at the RP2D of daily doses of 320 mg or 500 mg.
Safety and tolerability were the trial’s primary end point. The trial’s secondary end point was 24-week MMR rate and pharmacokinetics.
Baseline characteristics from the trial showed that patients had a median age of 57 years (range, 29-86), and most had discontinued their last TKI treatment due to a lack of efficacy (64%). Other patients in the trial had discontinued their last TKI treatment due to lack of tolerability (29%) or other reasons (8%). Patients had a median of 3 prior lines of TKIs (range, 1-6), with most patients receiving 3 or more prior TKIs (60%). Moreover, some patients had received prior asciminib (38%) and ponatinib (22%).
In the first dose-escalation phase of the study, patients (n = 38) achieved an overall MMR of 74% (95% CI, 56.9%-86.6%), with 64% (95% CI, 44.1%-81.4%) of patients achieving MMR by 24 weeks (n = 28), and 100% (95% CI, 69.2%-100%) of evaluable patients maintaining MMR for at least 24 weeks (n = 10).
Regarding safety, TERN-701 was well tolerated and demonstrated a favorable safety profile, with 81% of patients (n = 63) experiencing any-grade treatment-emergent adverse effects (TEAEs) and 32% experiencing grade 3 or higher TEAEs. No dose-limiting toxicities were reported, and 1 patient (2%) discontinued treatment due to TEAEs. Common any-grade TEAEs that occurred in at least 10% of all patients were thrombocytopenia (16%), neutropenia (13%), diarrhea (21%), headache (19%), nausea (19%), fatigue (14%), and abdominal pain (13%). Common grade 3 or higher TEAEs were thrombocytopenia (8%), neutropenia (8%), and leukopenia (3%).
