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J.B. Trepel
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OA18 - New Insights in the Treatment of Thymic Malignancies (ID 408)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:N. Girard, S.B. Watzka
- Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 2
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OA18.02 - Evaluation of a Modified Dosing Regimen (2-Weeks on/1-Week off) of Sunitinib as Part of a Phase II Trial in Thymic Carcinoma (ID 6289)
11:00 - 12:30 | Author(s): J.B. Trepel
- Abstract
- Presentation
Background:
Sunitinib is active in patients with recurrent thymic carcinoma (TC). We have previously reported an objective response rate of 26% and disease control rate (partial response and stable disease) of 91% in patients with TC when sunitinib is administered at a dose of 50 mg once daily for 4 weeks followed by 2 weeks off (4/2 dosing schedule). Grade 3 or 4 treatment-related adverse events (TEAEs) occurring in more than 10% of patients included fatigue, oral mucositis and lymphocytopenia (20% each), and hypertension (13%). Grade 3 decrease in left ventricular ejection fraction (LVEF) was observed in 8% of patients. Alternative dosing schedules have been evaluated in solid tumors to improve tolerability. As part of an ongoing phase II study (NCT01621568), we evaluated the clinical activity and tolerability of sunitinib in patients with TC using a 2-weeks-on/1-week-off (2/1) dosing regimen.
Methods:
Patients with progressive TC after at least one prior platinum-containing chemotherapy regimen, measurable disease, and adequate end organ function were enrolled and received sunitinib at a dose of 50 mg orally once daily using a 2/1 schedule until disease progression or development of intolerable adverse events. The primary objective was evaluation of response rate. Tumor assessments were performed every 6 weeks using RECIST version 1.1 and toxicity was assessed every 3 weeks using CTCAE version 4.0. Exploratory correlative studies including evaluation of immune cell subsets will be reported separately.
Results:
Between July 8, 2014 and January 14, 2016, 15 patients were enrolled. Median age was 62 years (range, 41-76), and 33% were male. A median of 4 (range, 1 – 33+) cycles of sunitinib was administered. Among 13 evaluable patients, there was 1 (8%) partial response, 11 (85%) stable disease and 1 (8%) progressive disease. After a median follow-up of 16 months, the median progression-free survival was 5 months and median overall survival was 16 months. Grade 3 or 4 TEAEs occurring in more than 10% of patients included lymphocytopenia (40%), neutropenia and leucopenia (20% each), thrombocytopenia and oral mucositis (13% each). Grade 3 decrease in LVEF was observed in 1 (7%) patient.
Conclusion:
Sunitinib, administered using a 2/1 dosing schedule, has clinical activity in patients with TC, and the frequency of clinically significant TEAEs (fatigue, mucositis, hypertension) is acceptable. Studies are ongoing to identify novel immunological biomarkers of activity.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-031 - QUADRUPLE THREAT: A Pilot Phase 2 Study of RRx-001 in Advanced Lung Cancer Prior to Re-Administration of Platinum Doublets (ID 5080)
14:30 - 15:45 | Author(s): J.B. Trepel
- Abstract
Background:
The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. RRx-001, an epi-immunotherapeutic agent, may resensitize patients to previously effective, now refractory therapies, potentially improving survival. This study (NCT02489903) explores the potential of RRx-001 to sensitize patients who previously responded and now have failed a platinum based doublet to the previously effective therapy.
Methods:
In this 4-arm, 3-stage study, subjects with SCLC, NSCLC, HGNEC and ovarian cancer (EOC) in each arm receive RRx-001 weekly until progression followed by platinum therapy. Each cohort will initially enroll 3 patients to assess for safety (Stage 1) then 7 patients (Stage 2) for a total of 10 patients per cohort. If any arm has > 1/10 subjects that has stable disease or better, then additional patients would be enrolled in that arm (Stage 3) for totals of 31 (NSCLC), 26 (SCLC), 26 (HGNEC) and 26 (EOC). Eligibility criteria include: evaluable, progressive disease; previous response to platinum doublet therapy; ECOG PS ≤2. Primary endpoint is Overall Survival with ORR, DCR, PFS and rate of toxicity for reintroduced platinum therapy as secondary endpoints. Exploratory pathologic assessments, including oncogenic mutation expression and infiltrating tumor lymphocyte analysis, will be performed on tumor samples before and after starting the study regimens.
Results:
Stage 1 for all arms except EOC has been completed with no unexpected AEs. RRx-001 treatment to date resulted in a 45% (5/11) DCR including one Partial Response in HGNET. Reintroduction of platinum therapy in evaluable patients with SCLC and NSCLC resulted in an ORR of 75% (3/4), and 67% (2/3), respectively (HGNET and EOC: 0 evaluable). Median OS for all patients is 7.0 mo. (7.8 mo. median f/u). One patient with resistant SCLC had a confirmed Partial Response to cisplatin/etoposide and his treatment free interval post platinum was >180 days. To date, serial on-treatment biopsies have demonstrated an increase in T-cell tumor infiltration over time. Recruitment to this study is continuing.
Conclusion:
Although the trial is ongoing, early data suggest that RRx-001 appears to increase the sensitivity of SCLC and NSCLC to subsequently reintroduced carboplatin or cisplatin (to date no HGNCEC and EOC patients have been rechallenged with platinum). In addition, data from one patient indicates a conversion of resistant to sensitive SCLC phenotype. These data suggest that RRx-001 priming may lead to a new treatment strategy resulting in renewed sensitivity to chemotherapy and prolongation of survival.
