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S. Mocci



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    OA 17 - Immunotherapy II (ID 683)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      OA 17.02 - Updated Efficacy Results From the BIRCH Study: First-Line Atezolizumab Therapy in PD-L1–Selected Patients With Advanced NSCLC (ID 8006)

      14:30 - 16:15  |  Author(s): S. Mocci

      • Abstract
      • Presentation
      • Slides

      Background:
      The anti–PD-L1 mAb atezolizumab blocks the interactions between PD-L1 and its receptors, PD-1 and B7.1, thus restoring anti-tumor immunity. A Phase II study of atezolizumab monotherapy was conducted across multiple lines of therapy in PD-L1–selected patients with advanced NSCLC (BIRCH; NCT02031458). The primary analyses showed meaningful and durable clinical benefit with atezolizumab monotherapy in 1L and 2L+ NSCLC. Here we present updated survival data (median follow-up, 29.7 months) in patients receiving 1L atezolizumab.

      Method:
      Eligible patients had chemotherapy-naive, locally advanced or metastatic NSCLC without CNS metastases. Prior TKI therapy was required in patients with EGFR mutation or ALK rearrangement. PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) was centrally evaluated (VENTANA SP142 IHC assay). Patients who were TC2/3 or IC2/3 (PD-L1 expression on ≥ 5% of TC or IC) were enrolled. Atezolizumab 1200 mg was administered IV q3w until disease progression or unacceptable toxicity. The primary endpoint was independent review facility (IRF)–assessed ORR. Secondary endpoints included investigator (INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.

      Result:
      With a median follow-up of 29.7 months, median OS was 26.9 months (TC3 or IC3 subgroup) and 24.0 months (all treated patients); INV-assessed ORR was 35% (TC3 or IC3 subgroup) and 26% (all treated patients; Table). Among evaluable patients, the ORR was 31% for mutant EGFR (4/13) vs 23% for wild-type EGFR patients (24/103), and 31% for mutant KRAS (10/32) vs 24% for wild-type KRAS patients (16/66). No new safety signals were observed.

      Conclusion:
      With more than 2 years of follow-up, atezolizumab continued to demonstrate durable clinical activity in 1L NSCLC, regardless of EGFR and KRAS mutational status. These data suggest that atezolizumab monotherapy has promising activity as a frontline therapy. Ongoing Phase III trials are evaluating atezolizumab-based regimens vs chemotherapy in 1L NSCLC.

      Endpoint (95% CI) TC3 or IC3[a ](n = 65) TC2 or IC2[b] (n = 73) All Treated Patients (N = 138)
      INV-assessed ORR, % 35% (23.9, 48.2) 18% (9.8, 28.5) 26% (19.0, 34.2)
      EGFR mutant/wild-type, % 25%/33% 33%/15% 31%/23%
      KRAS mutant/wild-type, % 38%/33% 25%/15% 31%/24%
      mDOR, mo 16.5 (8.5, NE) 12.5 (8.3, 17.9) 13.1 (9.9, NE)
      mOS, mo 26.9 (12.0. NE) 23.5 (18.1, NE) 24.0 (18.1, 31.9)
      12-mo OS rate, % 61% (49.0, 74.0) 71% (59.8, 81.5) 66% (58.1, 74.6)
      24-mo OS rate, % 52% (39.3, 65.2) 49% (37.0, 61.1) 50% (41.5, 59.2)
      30-mo OS rate, % 48% (35.3, 61.5) 39% (27.2, 51.2) 43% (34.3, 52.1)
      mPFS, mo 7.3 (4.9, 12.0) 7.6 (4.0, 9.7) 7.6 (5.7, 9.7)
      12-mo PFS rate, % 38% (25.1, 49.9) 30% (19.2, 41.2) 34% (25.3, 41.9)
      24-mo PFS rate, % 28% (16.5, 40.0) 13% (4.5, 21.5) 20% (12.9, 27.5)
      30-mo PFS rate, % 19% (5.4, 33.5) 9% (1.4, 16.4) 14% (6.5, 21.9)
      NE, not estimable. [a ]TC ≥ 50% or IC ≥ 10% PD-L1–expressing cells.[b ]TC2/3 or IC2/3 excluding TC3 or IC3.


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    P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      P1.04-011 - Development of Novel Blood-Based Biomarker Assays in 1L Advanced/ Metastatic NSCLC: Blood First Assay Screening Trial (BFAST) (ID 8398)

      09:30 - 16:00  |  Author(s): S. Mocci

      • Abstract
      • Slides

      Background:
      Worldwide it is estimated that 20%-30% of advanced NSCLC patients do not receive a complete molecular diagnosis at baseline and are ineligible for targeted therapies due to tissue biopsy limitations. Blood-based, multiplex testing that analyzes circulating tumor DNA (ctDNA) by targeted next-generation sequencing offers a minimally invasive testing method, but clinical utility has yet to be established. High tumor mutational burden (TMB) measured in tissue is associated with atezolizumab (anti–PD-L1) clinical activity in several tumor types, including NSCLC. Alectinib, a potent, selective ALK/RET kinase inhibitor, has shown activity in 1L and is approved as 2L therapy in patients with ALK- or RET-positive advanced NSCLC but requires tissue for analysis. Here we present an umbrella trial that aims to clinically validate novel blood-based diagnostic assays that measure TMB in the blood (bTMB) and somatic mutations (e.g., ALK/RET), and to determine the efficacy and safety of 1L atezolizumab or alectinib in biomarker-selected NSCLC patients.

      Method:
      BFAST is a Phase II/III global, multicenter, open-label, multi-cohort screening and interventional umbrella trial designed to evaluate the safety and efficacy of targeted therapies in patients with unresectable, advanced or metastatic NSCLC selected based on the presence of oncogenic somatic mutations or a positive bTMB score. Key eligibility criteria include previously untreated, stage IIIB-IVB NSCLC of any histology and measurable disease per RECIST v1.1. Pre-enrollment blood-based screening will identify patients whose tumors harbor oncogenic somatic mutations (ALK/RET) or a positive bTMB score (above a pre-specified cutoff); patients will be assigned to the appropriate cohort based on the screening results. Study treatment will continue until disease progression (all cohorts) or loss of clinical benefit (atezolizumab only) (Table). The modular trial design allows for additional biomarker-driven BFAST cohorts with distinct screening and treatment requirements, and endpoints such as ORR with highly active drugs.

      Table. BFAST Study Details
      Cohort Treatment Planned Enrollment, n Primary Endpoints Key Secondary Endpoints
      Cohort AALK+ Alectinib 600 mg PO bid 78 ORR per RECIST v1.1 (INV-assessed) DOR, CBR[c] and PFS per RECIST v1.1 (INV-assessed) ORR, DOR, CBR and PFS per RECIST v1.1 (IRF-assessed) OS
      Cohort B RET+ Alectinib 900 and 1200 mg dose escalation 52-62 ORR per RECIST v1.1 (INV-assessed) DOR, CBR and PFS per RECIST v1.1 (INV-assessed) ORR, DOR, CBR and PFS per RECIST v1.1 (IRF-assessed) OS
      Cohort C bTMB+ Atezolizumab 1200 mg IV q3w or platinum-based chemotherapy[a] ≈440 (R, 1:1)[b] PFS per RECIST v1.1 (INV-assessed) OS PFS, ORR and DOR per RECIST v1.1 (IRF-assessed) ORR and DOR per RECIST v1.1 (INV-assessed) 6- and 12-month PFS rates
      [a ]Cisplatin or carboplatin + pemetrexed for non-squamous histology, and cisplatin or carboplatin + gemcitabine for squamous histology. Administered per standard of care. [b ]Stratification factors include tissue availability, ECOG performance status, bTMB level and tumor histology. [c ]CBR is defined as the rate of patients with confirmed CR or PR or stable disease that has been maintained for ≥ 24 weeks. bid, twice a day; bTMB, blood tumor mutational burden; CBR, clinical benefit rate; INV, investigator; IRF, independent review facility; IV, intravenously; PO, orally; q3w, every 3 weeks; R, randomized.


      Result:
      Section not applicable

      Conclusion:
      Section not applicable

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