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Giuseppe Giaccone
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OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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OA11.07 - Discussant - OA 11.04, OA 11.05, OA 11.06 (ID 14567)
14:35 - 14:50 | Presenting Author(s): Giuseppe Giaccone
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-47 - Phase I/II Trial of Dasatinib and Osimertinib in Patients with Advanced EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 14220)
16:45 - 18:00 | Author(s): Giuseppe Giaccone
- Abstract
Background
The presence of epidermal growth factor receptor (EGFR) mutations is associated with sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs), but a subset of patients (pts) do not respond to EGFR-TKIs or have very short duration of response, suggesting intrinsic resistance. Moreover, acquired resistance to EGFR-TKIs is inevitable for most patients. We showed that overexpression of Cripto-1, a member of the EGF–CFC family, contributes to the development of intrinsic resistance to EGFR-TKIs through the activation of the Src pathway and that the combination of EGFR-TKI therapy and Src inhibition works synergistically in preclinical models.
a9ded1e5ce5d75814730bb4caaf49419 Method
This was an open-label, phase I/II trial of osimertinib and dasatinib, a multi-kinase inhibitor with activity against Src, in EGFR-TKI treatment-naïve pts with advanced EGFR-mutant NSCLC (NCT02954523). Pts with pleural or pericardial effusions at study entry were excluded. The primary endpoint of the phase I part was to establish a safe and tolerable phase II dose of osimertinib and dasatinib. Dose escalation included 2 dose levels (dose level 1: osimertinib 80 mg QD, dasatinib 50 mg BID, dose level 2: osimertinib 80 mg QD, dasatinib 70 mg BID). In addition, 2 dose levels below the starting dose level could be explored if dose reductions were necessary.
4c3880bb027f159e801041b1021e88e8 Result
7 pts (4 at dose level 1, 3 at dose level 2) were enrolled to date. None of them had dose limiting toxicities (DLTs), but given frequent dose reductions and toxicities beyond the DLT period at dose level 2, dose level 1 is being further assessed (up to 6 pts at dose level 1). The most common treatment-related adverse events (TRAEs) included pleural effusion (n=6), AST elevation (n=5), ALT elevation (n=5), rash (n=5), and diarrhea (n=4), most of which were grade 1 or 2. 3/2/1 pts had grade 1/2/3 pleural effusion, respectively. 4 pts had grade 3 TRAEs, which included pleural effusion, fatigue, neutropenia, anemia, and headaches. No grade 4 or 5 toxicities were observed. Among 6 evaluable pts, 4 confirmed partial response (PR)/1 unconfirmed PR/1 stable disease were observed. Responses were durable with all the PRs ongoing.
8eea62084ca7e541d918e823422bd82e Conclusion
The combination of dasatinib and osimertinib showed no new safety signals and demonstrated evidence of anticancer activity. Treatment-related toxicities were manageable with dasatinib dose reductions and supportive measures. The safety and efficacy of dasatinib and osimertinib will continue to be explored.
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P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.12-03 - Phase I/II Trial Of 177Lu-DOTA0-Tyr3-Octreotate (Lutathera) And Nivolumab for Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (ID 12015)
16:45 - 18:00 | Author(s): Giuseppe Giaccone
- Abstract
Background
Despite initial sensitivity to chemotherapy, most patients with ES-SCLC relapse quickly. Studies have shown that somatostatin receptors are expressed in SCLC. Lutathera is a 177Lutetium-labeled somatostatin analog that targets somatostatin receptor positive cancer cells, which is approved for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Lutathera and nivolumab, an anti-PD-1 antibody, may have synergistic effects on the generation of anticancer immunity and this combination given as maintenance treatment may delay progression in patients with ES-SCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a multicenter phase I/II trial of Lutathera and nivolumab in patients with ES-SCLC (NCT03325816). The phase I portion includes patients with either relapsed/refractory ES-SCLC or non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary neuroendocrine tumors. The primary objective is to determine the recommended phase 2 dose (RP2D) of Lutathera when given with nivolumab. The phase I portion follows the standard 3+3 design, assessing two dose levels (dose level 1: Lutathera 3.7 GBq Q8W for 4 doses with nivolumab 240 mg Q2W; dose level 2: Lutathera 7.4 GBq Q8W for 4 doses with nivolumab 240 mg Q2W). In the phase II portion, patients with ES-SCLC not progressing after completion of first-line platinum-based chemotherapy are randomly assigned to either maintenance combination with Lutathera and nivolumab or observation. The primary endpoint for the phase II part is progression-free survival. Crossover is allowed at progression for those assigned to the observation group.
4c3880bb027f159e801041b1021e88e8 Result
Three patients were enrolled at dose level 1. All patients had ES-SCLC at study entry with 2 patients with progressive disease and 1 patient with stable disease after platinum-based chemotherapy. No dose-limiting toxicities (DLTs) were observed at dose level 1. Treatment-related adverse events include anemia (n=1), arthralgia (n=1), and non-cardiac chest pain (n=1), all of which were grade 1 events per CTCAE 4.03. At first tumor assessment performed 8 weeks after starting treatment, one patient achieved a partial response and two patients had progressive disease per RECIST. Assessment of dose level 2 is underway. Updated safety and efficacy results will be presented.
8eea62084ca7e541d918e823422bd82e Conclusion
Early evidence from the phase I/II trial of Lutathera and nivolumab suggests that the combination is safe, well tolerated and showed initial signs of antitumor activity. The safety and efficacy of the combination will be further explored.
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