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B.H. Childs



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    OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Mesothelioma
    • Presentations: 1
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      OA 02.01 - Randomized Phase II Study of Anetumab Ravtansine or Vinorelbine in Patients with Malignant Pleural Mesothelioma (ID 9377)

      11:00 - 12:30  |  Author(s): B.H. Childs

      • Abstract
      • Presentation
      • Slides

      Background:
      Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. We report the results of a randomized phase II trial of anetumab ravtansine compared to vinorelbine in patients with advanced malignant pleural mesothelioma (MPM) who have high mesothelin expression and have progressed on platinum/pemetrexed-based first-line chemotherapy (NCT02610140).

      Method:
      Patients (≥18 years) with locally advanced or metastatic MPM with progressive disease following first-line treatment with pemetrexed-based chemotherapy, with or without bevacizumab, were eligible. Patients were pre-screened based on obligatory tumor staining for mesothelin as determined by the Ventana MSLN (SP74) immunohistochemistry assay. The primary efficacy endpoint was progression-free survival (PFS) per central radiologic review using modified RECIST criteria for MPM. Secondary objectives included overall survival, tumor response, and safety. Patients were randomized in a 2:1 ratio to anetumab ravtansine 6.5 mg/kg Q3W IV or vinorelbine 30 mg/m[2] QW IV.

      Result:
      A total of 166 patients were randomized to anetumab ravtansine and 82 to vinorelbine; 3 and 10 patients, respectively, not receiving treatment were included for efficacy but not safety assessments. The treatment arms were evenly balanced, with 73% male, 64% ECOG performance status 1, 96% epithelioid histology, and a mean 2.5 (±2.4) months since last progression. The median duration of treatment (anetumab vs vinorelbine) was 12.6 weeks (range 3-61) vs 13.0 weeks (range 1-43). Treatment-emergent grade (G) ≥3 adverse events (AEs) were seen in 85 (52.1%) and 53 (73.6%) of patients, respectively. G3/G4 neutropenia (22.2%/16.7%) occurred in the vinorelbine arm whereas corneal epitheliopathy (39.3% all grade, 1.8% G3) was distinct for the anetumab ravtansine arm. Serious AEs (any grade) were similar; 52 (31.9%) vs 25 (34.7%). Treatment-emergent AEs leading to dose modification were 42.9% in the anetumab ravtansine arm and 80.6% in the vinorelbine arm. There was one treatment-related G5 event in each arm. Median PFS was 4.3 months (95% CI:4.1, 5.2) for anetumab ravtansine vs 4.5 months (4.1, 5.8) for vinorelbine; hazard ratio 1.22 (0.85, 1.74), p=0.859. Fourteen (8.4%) patients in the anetumab ravtansine arm had an objective response vs 5 (6.1%) in the vinorelbine arm, with no complete responses. Interim median overall survival was 10.1 mo (7.6, -) vs 11.6 mo (7.7, 12.5), respectively, p-value 0.721.

      Conclusion:
      In relapsed MPM, anetumab ravtansine was not superior to vinorelbine with respect to PFS.

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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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      P1.04-013 - Phase 1b Multi-Indication Study of the Antibody Drug Conjugate Anetumab Ravtansine in Patients with Mesothelin-Expressing Advanced or Recurrent Malignancies (ID 10897)

      09:30 - 16:00  |  Author(s): B.H. Childs

      • Abstract
      • Slides

      Background:
      Mesothelin is expressed in a wide variety of tumors, including mesothelioma, ovarian, pancreatic, gastric/GEJ, NSCLC, triple-negative breast cancer, cholangiocarcinoma, and thymic carcinomas. Anetumab ravtansine (BAY 94-9343), is a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4 and has shown encouraging anti-tumor activity in mesothelioma and ovarian cancer patients in a phase I study. We will therefore conduct a signal generating study with anetumab ravtansine in six additional high unmet medical need malignancies with mesothelin expression (NCT03102320).

      Method:
      Eligibility criteria include: ≥18 years, unresectable locally advanced or metastatic recurrent or relapsing disease, one or more prior lines of therapy, and availability of tumor tissue for mesothelin expression testing. Mesothelin-positive patients with selected adenocarcinomas (NSCLC, triple negative breast, gastric including gastroesophageal junction) and thymic carcinoma will receive anetumab ravtansine as monotherapy at 6.5 mg/kg IV on a 21-day cycle. Patients with cholangiocarcinoma will receive anetumab ravtansine in combination with cisplatin (25 mg/m2 IV day 1 and 8 on a 21-day cycle for up to 6 cycles) and patients with pancreatic adenocarcinoma will receive anetumab ravtansine in combination with gemcitabine (1000 mg/m2 IV day 1 and 8 on a 21-day cycle). A safety run-in phase (18-24 patients each) will be conducted for the combination regimens prior to enrolling patients in the main study phase. The primary objective of the main phase of the study is objective response rate (ORR) of anetumab ravtansine as monotherapy or combination therapy in patients with either of two mesothelin expression levels: high (≥30% positive tumor cells with moderate and stronger membrane staining intensity) and low-mid (≥5% all intensities and <30% positive tumor cells with moderate and stronger membrane staining intensity). Secondary objectives include safety, disease control rate, duration of response, durable response rate, and progression-free survival. Approximately 348 patients will be enrolled.

      Result:
      Section not applicable

      Conclusion:
      Section not applicable

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