- LCL161 is a targeted experimental therapy that induces tumor necrosis factor (TNF)-mediated apoptosis in models of triple-negative breast cancer (TNBC).
- In this phase 2 trial, LCL161 enhanced the efficacy of paclitaxel in patients with TNBC with a TNF-based gene expression signature (GS), but not in patients without the signature.
Why this matters
- Findings are promising enough to warrant progression to a phase 3 trial.
- Randomized controlled phase 2 trial of 209 patients with localized TNBC (T2/N0-2/M0).
- Patients were divided into GS-positive and GS-negative groups; each group was randomly assigned to oral LCL161 (1800 mg/week) and intravenous paclitaxel (80 mg/m2 once weekly; combination group) or paclitaxel alone (control group) for 12 weeks, followed by surgery.
- Primary outcome: >7.5% increase in pathologic complete response (pCR) over control group.
- Funding: Novartis.
- GS-positive group: pCR rate was greater in the combination than the control group (38.2% vs 17.2%), with 88.8% posterior probability of >7.5% increase in pCR.
- GS-negative group: pCR rate was lower in the combination group (5.6% vs 16.4%), with 0% posterior probability of >7.5% increase in pCR.
- The combination group had higher rates of grades 3/4 neutropenia (24.5% vs 3.9%) and diarrhea (5.7% vs 1.0%).
- Blinding not specified.
- No survival outcomes studied.