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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
MA09.09 - First-In-Human Phase 1 Study of ABBV-399, an Antibody-Drug Conjugate (ADC) Targeting C-Met, in Patients with Non-Small Cell Lung Cancer (NSCLC) (ID 5008)
14:20 - 15:50 | Author(s): E. Angevin
The c-Met receptor is overexpressed in ~50% of patients with NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data support ABBV-399 as a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells.
In a 3+3 dose-escalation design, ABBV-399 was administered at doses ranging from 0.15 to 3.3 mg/kg once every 21 days to patients with advanced metastatic solid tumors (NCT02099058). ABBV-399 was then studied in a dose-expansion cohort in 16 patients with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) NSCLC that had progressed on ≥2 prior lines of therapy. ABBV-399 was also studied in combination with erlotinib in 10 patients with NSCLC, 8 of whom were c-Met+. Overexpression of c-Met was assessed by an IHC assay utilizing the SP44 antibody (Ventana; Tucson, AZ, USA).
As of June 27, 2016, 48 patients with solid tumors received ≥1 dose of ABBV-399. The dose-limiting toxicity (DLT) for ABBV-399 was febrile neutropenia, which occurred in 2 patients (1 each at 3 and 3.3 mg/kg). There were no treatment-related deaths. Monotherapy treatment-related adverse events (AEs) occurring in ≥10% of patients (including all dose levels and all grades) were fatigue (25.0%), nausea (22.9%), neuropathy (14.6%), decreased appetite (12.5%), vomiting (12.5%), and hypoalbuminemia (10.4%). Based primarily on safety and tolerability, a 2.7-mg/kg dose was chosen for dose expansion in patients with c-Met+ advanced NSCLC. Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC patients had a confirmed partial response (PR) with duration of response (DOR) 3+, 3, and 4.5 months. At week 12, 6 of 16 patients treated (37.5%) had disease control. Ten patients received ABBV-399 in combination with erlotinib. No DLTs were observed and AEs related to ABBV-399 occurring in ≥2 patients were acneiform rash (40.0%), fatigue (30.0%), and dry skin (20.0%). Three of 8 (37.5%) evaluable ABBV-399 + erlotinib-treated c-Met+ patients had a confirmed PR with DOR 2+, 4+, and 5+ months. Two of the 3 patients with PR had EGFR-mutated tumor, and previous TKI- and platinum-based chemotherapy had failed.
ABBV-399 is well tolerated at a dose of 2.7 mg/kg every 21 days and has demonstrated antitumor activity in patients with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated data of antitumor activity and safety of ABBV-399 as monotherapy and in combination with erlotinib in c-Met+ NSCLC patients will be presented.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
P1.06-044 - Costs of Adverse Events (AE) Associated with Cancer Therapies in Non-Small Cell Lung Cancer (NSCLC) in France (ID 5970)
14:30 - 15:45 | Author(s): E. Angevin
AE associated with existing and future treatments in NSCLC are frequent and should be accounted for in health economic models. In addition to utility decrements, appropriate costing of AE management is needed. In the case of NSCLC which affects 45 200 patients per year in France, published data are scarce and not always complete. It was therefore thought of importance to assess resource use and costs associated with AEs.
When looking at the grade 3 or 4 AEs appearing for at least 1% of patients in the clinical trials for erlotinib (TITAN, LUX-LUNG 8), ramucirumab plus docetaxel (REVEL), docetaxel and pembrolizumab (KEYNOTE 010), a list of 20 grade 3 and 4 AE was identified as relevant for Health Economic analysis. Among them, 7 did not have cost data available in the literature. Three French oncology experts were consulted. A questionnaire was sent before the meeting with the experts, asking for, according to the grade, insight on resource use (hospitalisation, follow-up visits, diagnosis exams, treatments). Results were discussed during the meeting in order to reach a consensus. Direct medical cost per AE, expressed in 2016 Euros, was then calculated from a national health insurance perspective based on public and private weighted tariffs and 2014 PMSI database.
The mean AE cost was €206 for thrombocytopenia, €263 for ocular toxic effect, €2,332 for arthralgia, €3,282 for venous thromboembolism, €3,732 for pulmonary bleeding, €5,176 for dehydration, €5,751 for pneumonia, infiltration or pneumonitis. Hospitalization costs corresponded to 46% to 100% of total AE cost. These AE costs were consistent with the costs of other grade ¾ AEs previously published for NSCLC therapies.
Among seven grade 3 and 4 AEs seen, four appear to have an important economic impact, with a management cost of at least €3,000 per event.