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M.E. Olmedo



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    MA09 - Immunotherapy Combinations (ID 390)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (ID 4712)

      14:20 - 15:50  |  Author(s): M.E. Olmedo

      • Abstract
      • Presentation
      • Slides

      Background:
      Trials of anti-EGFR necitumumab and anti-PD1 pembrolizumab demonstrate the anti-tumor activity of each agent in NSCLC.

      Methods:
      Single-arm, multicenter Phase 1b study to investigate effectiveness and safety of necitumumab combined with pembrolizumab in patients with Stage IV NSCLC (NCT02451930). In Part A, escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W. In the absence of dose limiting toxicity, Part B (expansion cohort) was planned with necitumumab 800 mg in 27 squamous and 27 nonsquamous NSCLC patients. Major eligibility criteria included: progression after ≥1 platinum-based chemotherapy, and ECOG PS 0-1. Study objectives were to evaluate tolerability and ORR by RECIST 1.1. PD-L1 status was centrally assessed using PD-L1 IHC 22C3 pharmDx assay (considered negative, weak positive, strong positive if <1%, 1-49%, ≥50% of tumor cells were stained, respectively).

      Results:
      The interim analysis population includes 34 nonsquamous patients (median age 61 years, 68% men, 21% never smokers, PD-L1 status: negative, 50% [17/34]; positive weak/strong, 15% [5/34]/15% [5/34]; unknown 21% [7/34[BJ1] ]). Median follow-up was 6.0 months. Ten patients (29.4%) had PR (confirmed and unconfirmed) (PRs by PD-L1 status: negative, 18% [3/17]; positive weak/strong, 60% [3/5]/40% [2/5]; unknown status, 2 patients). DCR was 67.6%. PFS rate at 6 months was 55.1% (95% CI, 36.2-70.6); median PFS was 6.9 months (95% CI, 2.7-NR). Most common Grade ≥3 AEs were skin rash (9%), hypomagnesemia (9%), VTE (9%) and increased lipase (9%); 1 patient died due to an AE (respiratory tract infection). Five patients (14.7%) discontinued therapy because of an AE. Figure 1



      Conclusion:
      Safety profile corresponds to individual profiles for both drugs, with no additive toxicities. These preliminary data suggest activity of this combination in a pretreated nonsquamous NSCLC population, irrespective of PD-L1 status.

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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-004 - Is There Any Role of Residential Radon in Non Small Cell Lung Cancer (NSCLC) Patients Harboring Molecular Alterations? (ID 4770)

      14:30 - 15:45  |  Author(s): M.E. Olmedo

      • Abstract

      Background:
      Radon gas is the first cause of lung cancer in non-smoking population. The World Health Organization (WHO) recommends radon concentration lower than 100 Bq/m3. In recent years, most of the advances in personalized therapy in NSCLC patients also occurred in non-smokers. Furthermore, limited information is available about the clinical and pathological characteristics in patients exposed to radon gas. We hypothesized that residential radon could be associated to some specific pathological and molecular alterations in NSCLC patients.

      Methods:
      Prospective study of a cohort of NSCLC patients harbouring molecular alterations (EGFR, BRAF mutations (m), ALK and ROS1 rearrangements (r)) in our centre, between September 2014 and October 2015. A radon detector alpha-track was given to each patient to measure residential radon concentration for 3 months; it was analysed using optical microscopy. We collected demographic information, smoking history, environmental exposure and clinical characteristics. The pathologic characteristics were prospectively revised by a lung cancer pathologist, including histology pattern, grade and inflammatory infiltrate. EGFR and BRAF mutation (m) were analyzed using quantitative real-time polymerase chain reaction (PCR) and ALK and ROS1 rearrangement by fluorescence in situ hybridization (FISH). Data was analyzed using IBM SPSS v.20.

      Results:
      60 detectors were delivered (10% missing), 48 patients were evaluated (89.6% living in Madrid). Median age 66.5 (29- 82); 33 (68.8%) females; 33 non-smokers (31.3% passive smokers and 35.4% childhood exposure) and 3 (6.3%) light smokers. 100% adenocarcinoma (35.4% mixte, 18.8% acinar, 10.4% solid, 8.3% papillary, 8.3% micropapilllary, 8.4% others and 10.4% unknown); EGFRm 36 patients, ALKr 10 patients and BRAFm 2 patients. Home characteristics measured: 79.2% flat (89.1% measurement at bedroom); building material: 89.6% bricks. Median length of stay was 28 years (2-55). Median height of house 2 floors (0-15). Median of radon concentration: 104 Bq/m3 (42- 915); 60.42% over WHO recommendation. By molecular alteration: EGFRm median 96 Bq/m3 (42-915), ALKr median 116 (64-852) and BRAFm median 125 (125). A significant association was observed between non-EGFR mutation and concentration over the WHO recommendation (p=0.044). In univariant analysis, radon concentration was associated with non-mucinous histology and low tumoral grade (p=0.033 and p=0.023, respectively).

      Conclusion:
      Our final results have shown no consistent association between residential radon and molecular alterations in NSCLC patients, but a trend has been suggested in ALKr and BRAFm. Large multicenter studies are needed to confirm this hypothesis.

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    P3.06 - Poster Session with Presenters Present (ID 492)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Trial Design/Statistics
    • Presentations: 1
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      P3.06-002 - ATLANTIS Trial: Phase III Study of PM01183/Doxorubicin vs. CAV or Topotecan in SCLC after One Platinum-Containing Line (ID 5877)

      14:30 - 15:45  |  Author(s): M.E. Olmedo

      • Abstract
      • Slides

      Background:
      PM01183 (lurbinectedin) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. Synergism in combination with doxorubicin with compelling overall response rates (~67%, including approximately 10% complete responses) was reported in a phase I expansion cohort in 21 second-line SCLC patients (pts) (ASCO 2015, abstract 7509). The most common toxicity observed was hematologic.

      Methods:
      Multinational, multicenter (>150 sites), open-label, randomized, phase III study of PM01183/doxorubicin vs. a control arm with investigator choice of either standard CAV or topotecan (1.5 mg/m[2], D1-5 q3wk). A total of 600 pts will be randomized (1:1) and stratified according to ECOG performance status (PS), chemotherapy-free interval (CTFI), known CNS involvement, prior PD-1/PD-L1 based immunotherapy and potential investigator’s control preference. Patients with clinical benefit after 10 cycles of doxorubicin containing-combination will continue on single agent PM01183 or CV, until PD or unacceptable toxicity. Interim safety analysis will be performed after 150 pts by an independent data monitoring committee. The most relevant inclusion criteria are: pts ≥18 years old; confirmed diagnosis of SCLC (small-cell carcinomas from unknown site are eligible provided ≥50% Ki-67 expression). One prior platinum containing regimen is mandatory (additional immunotherapy is allowed provided that it was not given in combination with CT); PS: 0-2 and adequate major organ function, including normal LVEF ≥50% at baseline. Pts are excluded if pre-treated with PM01183, doxorubicin or topotecan; symptomatic or steroid requiring CNS involvement or any serious medical condition that might preclude safe compliance with study treatment. The primary objective is to determine a difference in progression-free survival by an independent review committee. Secondary endpoints are overall survival, survival rates at 12/18/24 months, antitumor response (RECIST v1.1), duration of response, QoL, safety, subgroup analyses and pharmacokinetics (PK) of PM01183/doxorubicin arm. First patient is planned in JUL2016. Enrollment is expected to be completed by 4Q17.

      Results:
      Section not applicable

      Conclusion:
      Section not applicable

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