2019 ASCO-SITC: Combined Targeting of TIM-3 and PD-L1 Immune Checkpoint Pathways in Advanced Relapsed or Refractory Solid Tumors
A phase Ia/Ib trial was launched in order to evaluate the safety of LY3321367, an anti–T-cell immunoglobulin domain and mucin domain–containing molecule-3 (TIM-3) antibody, administered alone or in combination with LY3300054, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with advanced relapsed or refractory solid tumors. An analysis of the trial presented by Harding et al at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium (Abstract 12) focused on the safety, efficacy, pharmacokinetic, and pharmacodynamic results seen with these treatment regimens.
The ongoing, open-label, dose-escalation, and expansion study enrolled 41 patients with histologically confirmed advanced relapsed or refractory solid tumors. Patients were randomly assigned to receive intravenous infusions of LY3321367 at 3 mg to 1,200 mg alone once every 2 weeks (arm A), or at 70 mg to 1,200 mg in combination with LY3300054 once every 2 weeks (arm B). Primary objectives of the trial were assessment of the safety and tolerability of the regimen, as well as dose-limiting toxicity.
Findings
At data cutoff, 23 patients were in arm A and 18 patients were in arm B. Patients in arm B had received combination therapy as phase Ia dose escalation (median follow-up = 3 months).
Treatment-related adverse events were mild (grade ≤ 2) in both treatment groups, except for 1 patient with grade 3 anemia in arm B (200 mg of LY3321367 plus 700 mg of LY3300054). No dose-limiting toxicities, dose limiting–equivalent toxicities, treatment-related serious adverse events, or death were observed in either treatment arm.
Approximately 68% of patients in arm A and 88% of patients in arm B were positive for treatment-emergent antidrug antibodies related to LY3321367. Despite antidrug antibodies, no effect on pharmacokinetics was noted; antidrug antibody titers were generally low. In arm A, 2 patients had > 20% tumor regression, one of which was later confirmed as a partial response.
The authors concluded, “LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The [dose-limiting toxicity] for LY3321367 combination therapy is 1,200-mg intravenous infusions [once every 2 weeks] for cycles 1–2; 600-mg infusions [once every 2 weeks] starting at cycle 3 onward.”
Disclosure: The study authors' full disclosures can be found at coi.asco.org.
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