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Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors.
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2018
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Tumor-associated MacrophagesBreast OncologyAntitumor ActivityImmunologyPathologyImmunotherapeuticsAdvanced TumorsOncologyTumor ImmunityAnti-cancer AgentRadiation OncologyMolecular OncologyImmune SurveillanceCancer TreatmentPhase Ii DoseImmune Checkpoint InhibitorBreast CancerPhase Ib/ii StudyMedicine
3014 Background: Tumor-associated macrophages mediate intrinsic/acquired resistance to programmed death-1 (PD-1) inhibitors; these cells can be reduced by inhibiting the colony-stimulating factor-1 (CSF-1)/receptor pathway. Targeting CSF-1 with lacnotuzumab (MCS110), a high-affinity, humanized mAb, combined with spartalizumab (PDR001), a humanized anti-PD-1 mAb, is hypothesized to result in synergistic antitumor activity. Methods: This Phase Ib/II study (NCT02807844) assesses lacnotuzumab with spartalizumab in pts with advanced melanoma, endometrial, pancreatic (PC), or triple-negative breast cancer. During dose escalation, pts received lacnotuzumab at 1 or 3 mg/kg with 100 mg spartalizumab, or 3, 5, 7.5, or 10 mg/kg lacnotuzumab with 300 mg spartalizumab, every 3 weeks. For the Phase Ib part, primary endpoints are safety, tolerability, and recommended Phase II dose; secondary endpoints include antitumor activity and PK. Tumor biopsies are collected before and during treatment. Results: At data cut-off 24 Nov 2017, 50 pts (median age 60 years) were enrolled at 6 combination dose levels. The most common (≥30%) all-grade AEs regardless of study drug relationship were increased aspartate aminotransferase (AST; 32%), nausea (32%), vomiting (32%), asthenia (30%), and fatigue (30%); the most common (≥10%) Grade ≥3 AEs were increased AST (12%), asthenia (10%), and hyponatremia (10%). Frequent AEs suspected as drug-related were periorbital edema* (30%), increased AST (24%), and increased blood creatine phosphokinase (24%), which was the most frequent Grade ≥3 AE suspected as drug-related (6%). By RECIST 1.1, there was 1 partial response (PR); stable disease (SD) was 19% (9/48). By immune-related response criteria, disease control rate (irPR or irSD) was 27% (13/48); of note, 6/13 had PC. Out of 30 pts with PC, 1 pt achieved PR (on study for 346 days) and 2 pts had durable SD (on study for 328 and 319 days, respectively). PK and biomarker studies are ongoing. Conclusions: Lacnotuzumab with spartalizumab was well tolerated overall. Preliminary antitumor activity, notably in the PC cohort, was observed. Ongoing studies are evaluating this combination. *Includes eyelid edema and face edema. Clinical trial information: NCT02807844.