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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P1.01-083 - Phase 2 Study of MEDI4736 in Patients with PD-L1+ Locally Advanced or Metastatic Stage IIIb-IV NSCLC Treated with ≥ 2 Prior Regimens (ATLANTIC) (ID 2139)
09:30 - 17:00 | Author(s): M. Ballas
The role of third and further line therapies in advanced NSCLC is contentious both for patients harboring EGFR mutations and ALK translocations and for patients without activating mutations. Recent studies have demonstrated that activation of the EGFR pathway induces PD-L1 expression, thereby facilitating evasion of the host’s anti-tumor immune response as a potential mechanism of targeted therapy resistance. This evidence suggests a promising and inadequately explored role of immunotherapy in this particular setting of patients in whom only targeted agents were considered of unique interest. For the ~85% of patients with non-squamous NSCLC without ALK/EGFR aberrations, single agent chemotherapy represents the only option with its associated poor results and chemotherapy-related toxicities. Many cancers co-opt the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway to evade immune-mediated tumor rejection. Encouraging clinical activity against several tumor types has been seen for anti-PD-L1/PD-1 monoclonal antibodies (mAbs), including the proven benefit of nivolumab in advanced refractory squamous NSCLC. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD-80 with high affinity and selectivity. Evidence of clinical activity for MEDI4736 in NSCLC has been observed in a Phase 1 study (Study 1108, NCT01693562), with initial data indicating that PD-L1 expression is associated with a higher objective response rate (ORR). A clinical development program of MEDI4736 in NSCLC is underway. Here we describe the ATLANTIC study (NCT02087423).
In this Phase 2, open-label, international, multicenter, non-comparative study, the efficacy and safety of MEDI4736 (10 mg/kg IV every 2 weeks for up to 12 months) is being assessed in patients with PD-L1[+] locally advanced or metastatic NSCLC (Stage IIIb–IV). The present study design includes three patient cohorts: 1) Cohort 1 (n=≥94): patients with EGFR mutations or ALK alterations; 2) Cohort 2 (n=≥94): patients with wild-type EGFR and ALK; 3) Cohort 3 (n=≥94): patients with wild-type EGFR/ALK and ≥90% of tumor cells PD-L1[+]. Cohorts 1 and 2 include patients whose tumor tissue samples have ≥25% of tumor cells with membrane staining for PD-L1. The PD-L1 status was tested according to the VENTANA proprietary assay. At the time the study was conceived, patients were initially included regardless of PD-L1 status. However, based on the observation that PD-L1 expression may enrich response to MEDI4736 (Study 1108), the trial was amended accordingly to include PD-L1[+] tumors only. Eligible patients must have an ECOG Performance Status of 0 or 1, and have received ≥2 prior systemic treatment regimens, including one platinum-based chemotherapy and a tyrosine kinase inhibitor if EGFR or ALK positive. The primary outcome measure is ORR (RECIST v1.1), based on independent central review. Secondary outcome measures will further assess efficacy (including disease control rate, duration of response, progression-free survival and overall survival), safety (CTCAE v4.03), tolerability, pharmacokinetics, and immunogenicity of MEDI4736. Patients will be recruited at ~100–150 sites across North America, Asia, and Europe.
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