Phase II Study of ABBV-399 (process II) in Patients with C-MET Positive Stage IV/recurrent Lung Squamous Cell Cancer (SCC): LUNG-MAP Sub-Study S1400K (NCT03574753).

9075 Background: Lung-MAP is a platform trial to assess targeted therapies in SCC. S1400K was designed to evaluate the response to ABBV-399, an antibody-drug conjugate targeting C-MET, in patients with C-Met positive SCC. Methods: Patients with previously treated SCC with c-MET positive tumors (H score ≥150, Ventana SP44 assay), PS≤1, adequate organ function, peripheral neuropathy ≤ grade (G) 2, edema ≤ G2, albumin ≥3 g/dL, hepatic involvement by tumor < 50%. Patients were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor (ICI) naïve) and cohort 2 (ICI refractory). ABBV-399 2.7 mg/kg was administered intravenously over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), response within cohort, duration of response (DoR), and toxicities associated with ABBV-399. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment. Results: Between 2/15/18 and 10/16/2018, 50 patients (17% of patients screened) were assigned to S1400K, 28 patients enrolled (15 in cohort 1 and 13 in cohort 2), 25 were determined eligible, of whom 23 received ABBV-399 and were assessed for adverse events. There were 3 G5 events (2 pneumonitis, both in cohort 2 and 1 bronchopulmonary hemorrhage) and 4 G3 events. S1400K was temporarily closed on 10/16/2018 for interim analysis and safety concerns, and formally closed on 12/21/2018. Two responses were reported, both in cohort 1 (1 complete and 1 unconfirmed partial response, CR and UPR) for a response rate of 9% (95% CI: 0-20%). The CR remains on treatment at 4 months and DoR for the UPR was 2.3 months. Ten patients had stable disease and disease control rate was 52% (3-73%). The median OS and PFS were 4.7 and 2.4 months. Conclusions: ABBV-399 failed to meet the pre-specified response needed to justify continuing enrollment. Pneumonitis was an unanticipated toxicity observed in patients with SCC with previous immunotherapy exposure. Clinical trial information: NCT03574753.