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Marc Matrana



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-18 - NET-001: A Phase II Study of ABI-009 in Metastatic Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System (Now Available) (ID 1391)

      08:00 - 18:00  |  Author(s): Marc Matrana

      • Abstract
      • Slides

      Background

      Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with limited systemic treatment options. Preclinical evidence has shown that the PI3K/AKT/mTOR signaling pathway plays a central role in the pathogenesis and progression of NETs. Clinical studies with the mTOR inhibitor, everolimus, demonstrated its safety and efficacy in the treatment of NET, however, patients will ultimately progress. A novel mTOR inhibitor, ABI-009 (albumin-bound rapamycin nanoparticles, nab-rapamycin), has a favorable safety profile and evidence of efficacy in patients with solid tumors and offers promise for NETs. A preclinical study showed significantly greater antitumor activity and prolonged survival with ABI-009 compared with equal weekly dosing of oral rapamycin and oral everolimus. This preclinical study demonstrated superior efficacy of ABI-009 to oral mTOR inhibitors and suggest that ABI-009 may result in disease control after everolimus failure. The goal of this phase II pilot study is to evaluate the utility of ABI-009 in NETs to warrant a full phase II clinical study.

      Method

      This pilot phase II trial is a prospective, open-label, single arm, single center trial evaluating the efficacy and safety of ABI-009 in patients with gastroenteropancreatic or lung NETs who have undergone prior treatment with everolimus. Patients with unresectable, metastatic grade 1 and 2 NETs of the gastroenteropancreatic system or lung who have progressed or have been intolerant to everolimus will be eligible for inclusion in this study. The study will enroll 10 patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. ABI-009 will be administered intravenously at 100 mg/m2 on days 1 and 8 of a 21-day cycle. Patients will be treated until disease progression. Tumor response will be assessed by computerized tomography scan at baseline then every 9 weeks for 1 year, then every 12 weeks thereafter until progression. The primary endpoint is disease control rate at 6 months measured by RECIST 1.1. Currently, 3 of the planned 10 patients have been enrolled. ClinicalTrials.gov Identifier: NCT03670030.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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    P2.12 - Small Cell Lung Cancer/NET (ID 180)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.12-05 - A Phase II Trial of Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Neuroendocrine Carcinoma (Now Available) (ID 1429)

      10:15 - 18:15  |  Author(s): Marc Matrana

      • Abstract
      • Slides

      Background

      Combination chemotherapy is the mainstay of treatment for patients with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEPNECs) and neuroendocrine carcinomas (NECs) of the lung. Pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb), has high specificity for binding to the programmed cell death 1 (PD-1) receptor thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). In combination with chemotherapy, pembrolizumab blocks the protective mechanism of cancer cells and allows the immune system to destroy them. Combination chemotherapy and pembrolizumab was recently FDA approved and ongoing trials are utilizing this or similar combinations with data demonstrating a promising safety profile. The purpose of this study is to test the efficacy, safety, and tolerability of combination chemotherapy with pembrolizumab in patients with high-grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve.

      Method

      This is an open label, phase II, single institution, multi-site trial using pembrolizumab in combination with either cisplatin or carboplatin and etoposide in patients with high grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. Patients with a histologic diagnosis of a GEPNECs with a Ki-67 of 55% or higher or a large cell NEC of the lung will be eligible for inclusion in this study. Subjects must be deemed unresectable and have not undergone prior chemotherapy for metastatic disease. Patients must also have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1, and a predicted life expectancy > 3 months.

      Approximately 36 GEPNEC patients will be enrolled with an exploratory LCNEC of the lung cohort of approximately 6 patients. Patients will receive pembrolizumab 200mg IV in combination with cisplatin 80 mg/m2 or carboplatin AUC 6 on day 1 and etoposide 100mg/m2 on days 1-3 of a 21-day cycle. Tumor response will be assessed by computerized tomography scan every 6 weeks calculated with the first CT within 7 days of initiation of treatment. RECIST 1.1 will be used for treatment decisions until there is evidence of progressive disease (PD). Those patients who have responsive or stable disease after 4-6 cycles of platinum-based chemotherapy will move to maintenance pembrolizumab every 3 weeks. The primary endpoint will be progression free survival (PFS) per RECIST 1.1. ClinicalTrials.gov Identifier: NCT03901378

      Result

      Section not applicable

      Conclusion

      Section not applicable

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    PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)

    • Event: WCLC 2019
    • Type: Plenary Session
    • Track:
    • Presentations: 1
    • Now Available
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      PL02.08 - Registrational Results of LIBRETTO-001: A Phase 1/2 Trial of LOXO-292 in Patients with RET Fusion-Positive Lung Cancers (Now Available) (ID 964)

      08:00 - 10:15  |  Author(s): Marc Matrana

      • Abstract
      • Presentation
      • Slides

      Background

      No targeted therapy is currently approved for patients with RET fusion-positive non-small cell lung cancer (NSCLC). LOXO-292 is a highly selective RET inhibitor with activity against diverse RET fusions, activating RET mutations and brain metastases. Based on initial data from LIBRETTO-001, LOXO-292 received FDA Breakthrough Designation for the treatment of RET fusion-positive NSCLC in August 2018.

      Method

      This global phase 1/2 study (87 sites, 16 countries) enrolled patients with advanced RET-altered solid tumors including RET fusion-positive NSCLC (NCT03157128). LOXO-292 was dosed orally in 28-day cycles. The phase 1 portion established the MTD/RP2D (160 mg BID). The phase 2 portion enrolled patients to one of six cohorts based on tumor type, RET alteration, and prior therapies. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, CNS ORR, CNS DoR, PFS, OS, safety and PK.

      Result

      As of 17-June 2019, 253 RET fusion-positive NSCLC patients were treated. The primary analysis set (PAS) for LOXO-292 registration, as defined with the US FDA, consists of the first 105 consecutively enrolled RET fusion-positive NSCLC patients who received prior platinum-based chemotherapy; 58 patients (55%) also received prior anti PD-1/PD-L1 agents. The majority of PAS responders have been followed for ≥6 months from first response. Of the remaining 148 patients, 79 had previously been treated with platinum-based chemotherapy, 55 did not receive prior platinum-based chemotherapy and 14 did not have measurable disease at baseline.

      Among PAS patients, the investigator-assessed ORR was 68% (95% CI 58-76%, n=71/105, 2 PRs pending confirmation). Responses did not differ by fusion partner or the type or number of prior therapies, including chemotherapy, anti PD-1/PD-L1 agents and multikinase inhibitors with anti-RET activity. The median DoR was 20.3 months (95% CI 13.8-24.0) with a median follow-up of 8 months; as evidenced by the wide confidence interval, this DoR estimate is not statistically stable due to a low number of events (16 of 69 confirmed responders). The intracranial ORR was 91% (n=10/11: 2 confirmed CRs, 8 confirmed PRs) for patients with measurable brain metastases at baseline.

      The ORR in efficacy evaluable treatment naïve RET fusion-positive NSCLC patients was 85% (95% CI 69-95%, n=29/34, 7 PRs pending confirmation). In the safety data set of all 531 patients, 5 treatment-related AEs occurred in ≥15% of patients: dry mouth, diarrhea, hypertension, increased AST and increased ALT. Most AEs were grade 1-2. Only 9 of 531 (1.7%) patients discontinued LOXO-292 for treatment-related AEs.

      Conclusion

      LOXO-292 had marked antitumor activity in RET fusion-positive NSCLC patients and was well tolerated. These data will form the basis of an FDA NDA submission later this year.

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