Safety and Immunogenicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive Non-Small-Cell Lung Cancer

Introduction: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy. Methods: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 g recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4). Results: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4(+) T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8(+) T-cell responses were only detected in four patients. Conclusion: In resected and unresectable NSCLC patients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses. GlaxoSmithKline Biologicals SA sponsored the clinical trial and covered the costs associated with the development and publishing of the manuscript, including scientific writing assistance. adjuvant chemotherapy; immunotherapy; immunostimulant; MAGE-A3; non–small cell lung carcinoma; vaccin

ceritinib plus nivolumab in patients with advanced alk rearranged non small cell lung cancer results of an open label multicenter phase 1b study

Abstract Introduction Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. Methods In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Results In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9–99.6) in the 450-mg cohort and 60% (95% CI: 26.2–87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7–84.3) in the 450-mg cohort and 25% (95% CI: 5.5–57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1–87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0–58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. Conclusion Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent

2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

This manuscript provides recommendations for the diagnosis, treatment and follow-up of early stage non-small cell lung cancer developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 201

2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines, ESMO organises consensus conferences to focus on specific issues. The 2nd ESMO Consensus Conference on Lung Cancer included 35 experts who met to address several questions on non-small-cell lung cancer (NSCLC). Recommendations were made with reference to grade of recommendation and level of evidence. This paper focuses on locally advanced diseas

Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).</p

2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease

This manuscript provides recommendations for first-line / second and further lines of treatment in advanced disease in non-small cell lung cancer (NSCLC). These recommendations were developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 201

Immune checkpoint inhibitors for every patient with non-small cell lung cancer? Update on immunotherapy in patients with lung cancer

status: publishe