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F. Braiteh
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-065 - Lack of Drug-Drug Interaction (DDI) between Necitumumab and Gemcitabine or Cisplatin: A Phase 2, Open-Label, Nonrandomized Study (ID 6195)
14:30 - 14:30 | Author(s): F. Braiteh
- Abstract
Background:
Necitumumab is a recombinant human immunoglobulin G1 monoclonal antibody that blocks the ligand-binding site of EGFR. This study evaluated the effects of necitumumab on the pharmacokinetics (PK) of gemcitabine and cisplatin, and compared the PK of 2 necitumumab drug products manufactured by 2 different processes: Process C and Process D.
Methods:
Study participants included adult patients with advanced or metastatic malignant solid tumors (except colorectal tumors with KRAS mutation) that were resistant to standard therapy or for which no standard therapy was available. Patients enrolled in 2 cohorts received intravenous (IV) infusions of necitumumab 800 mg (cohort 1: Process C drug product; cohort 2: Process D drug product) on Day 3 of the PK run-in period following IV infusions of gemcitabine 1250 mg/m[2] and cisplatin 75 mg/m[2] on Day 1 of the PK run-in period, and subsequent infusions (same doses) of gemcitabine on Days 1 and 8, cisplatin on Day 1, and necitumumab on Days 1 and 8 of each 3‑week cycle. The effect of necitumumab on the PK of gemcitabine and cisplatin was evaluated in the PK run-in period and cycle 1 of cohort 1, and the PK of Process C and D necitumumab drug products were compared in PK run-in periods of cohorts 1 and 2. Blood was drawn immediately before and at regular intervals after each infusion in the PK run-in period to determine concentrations of necitumumab, gemcitabine, and cisplatin for PK parameter computation. Study treatment could continue up to 6 cycles and was discontinued for disease progression, unacceptable toxicity, or other withdrawal criteria. Patients who had not progressed had an option to continue necitumumab monotherapy until withdrawal criteria were met.
Results:
Eighteen and 20 patients were enrolled in cohort 1 and cohort 2, respectively. Coadministration of necitumumab did not alter dose-normalized area under the plasma concentration curves (AUCs) of gemcitabine and cisplatin (geometric least squares mean [GLSM] ratios: 90% CI;1.184: 0.960‑1.459 and 1.105: 1.063-1.148, respectively). Similarly, coadministration of gemcitabine and cisplatin with necitumumab did not alter AUC of necitumumab (GLSM ratio:90% CI; 1.077: 0.988-1.174). PK exposure parameters for both Process C and Process D drug products were similar, with GLSM ratios for AUC close to 1 and 90% CIs within the range of 80‑125%. No new safety signals were reported.
Conclusion:
No clinically relevant DDIs between necitumumab and gemcitabine or cisplatin were observed. Process C and Process D drug products had similar PK profiles. ClinicalTrials.gov Identifier:NCT01606748; Funding: Eli Lilly.
