FDA BRIEF: Week of May 8, 2017
IMFINZI (durvalumab) injection
AstraZeneca. Wilmington, DE, USA
VENTANA PD-L1 (SP263) Assay
Ventana Medical Systems, Inc., Tucson, AZ, USA
INDICATION: Treatment of patients with locally advanced or metastatic urothelial carcinoma who:
- have disease progression during or following platinum-containing chemotherapy
- have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum containing chemotherapy.
REG PATHWAY: Accelerated Approval
- Based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials
- Also approval for complementary diagnostic for the assessment of the PD-L1 protein in formalin-fixed, paraffin-embedded urothelial carcinoma tissue
MECHANISM OF ACTION: Human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80; releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity
EFFICACY:
- Multicenter, multicohort, open-label clinical trial, n=182 patients with locally advanced or metastatic urothelial carcinoma; had progressed while on or after a platinum-based therapy
- Major efficacy outcome measures: Confirmed Objective Response Rate (ORR) according to RECIST v1.1 by Blinded Independent Central Review (BICR), and duration of response (DoR)
- Responding patients: 31; 45% had ongoing responses of 6 months or longer, 16% had ongoing responses of 12 months or longer
- Confirmed ORR: 26.3% in 95 patients with a high PD-L1 score, 4.1% in 73 patients with a low or negative PD-L1 score
SAFETY:
- Most common adverse reactions: Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection
- Infection and immune-related adverse events: Pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, diabetes
ALUNBRIG (brigatinib) tablets
Ariad Pharmaceuticals, Inc. (Takeda), Cambridge, MA, USA
INDICATION: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib
REG PATHWAY: BLA. Accelerated Approval, Breakthrough Therapy Designation, Orphan Drug Designation, Priority Review
- Accelerated approval based on tumor response rate and duration of response
- Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial
MECHANISM OF ACTION: Tyrosine kinase inhibitor with in vitro activity against multiple kinases, inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins, dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice
EFFICACY:
- Two-arm, open-label, multicenter trial, n=222, patients with locally advanced or metastatic ALK-positive NSCLC who had progressed on crizotinib, had documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization Probe Kit test. BRIGATINIB 90 mg or 180 mg
- Major efficacy outcome measure: Confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) evaluated by an Independent Review Committee (IRC); Additional measures included Investigator-assessed ORR, duration of response (DOR), intracranial ORR, and intracranial DOR
- ORR: 48% (90 mg), 53% (180 mg) with DOR of 13.8 months in both arms
- Intracranial ORR: 42% (90 mg), 67% (180 mg), DOR of at least 4 mo.
SAFETY:
- Most common adverse reactions: Nausea, diarrhea, fatigue, cough, headache
- Most common serious adverse reactions: Pneumonia and ILD/pneumonitis
- Fatal adverse reactions: Pneumonia, sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, urosepsis
Image Source: Google