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C. Aggarwal
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OA 14 - New Paradigms in Clinical Trials (ID 681)
- Event: WCLC 2017
- Type: Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Alex Adjei, Eun Kyung Cho
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 311 + 312
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OA 14.07 - Progress in Lung Squamous Cell Carcinoma from the Lung-MAP Master Protocol (S1400) Sub-Studies S1400A, S1400B, S1400C and S1400D (ID 9593)
12:05 - 12:15 | Author(s): C. Aggarwal
- Abstract
- Presentation
Background:
Lung-MAP (S1400) is a master umbrella protocol designed to establish genomic screening for previously treated squamous cell lung cancer patients (SqCCA), and independently evaluate targeted therapies with matching biomarkers and alternative therapies (designated non-match therapy) in patients without putative markers. The protocol opened June 16, 2014 with four biomarker-driven sub-studies and one non-match sub-study.
Method:
Eligibility stipulated advanced SqCCA, progressing after at least one prior platinum-based chemotherapy, PS 0–2, and EGFR/ALK wild-type. Tumor samples were required and analyzed for gene alterations by FoundationOne NGS assay (Foundation Medicine). The original biomarker and non-match studies were: S1400B evaluating taselisib for PI3K mutations, S1400C evaluating palbociclib for cell cycle gene alterations (CCGA), S1400D evaluating AZD4547 for FGFR mutations, S1400E evaluating rilotumumab and erlotinib for c-MET positive tumors, and S1400A evaluating durvalumab in patients with no matching biomarkers. The original design included randomization to a control arm, but was amended to a single-arm phase 2 design. The primary endpoint for each modified sub-study was response.
Result:
As of June 16, 2017 all original sub-studies have been closed to accrual; 1298 patients registered to the screening component of the trial and 486 patients have registered to a sub-study. Two new sub-studies have been launched and are currently accruing. Details of the completed sub-studies are included in the table.Sub-study Final Accrual Biomarker prevalence/% of sub-study registrations Closure Date Response to investigational therapy N (%) Status S1400A (non-match) Total: 116 Durvalumab: 78 Docetaxel: 38 NA/59% 12/18/15 Docetaxel arm closed: 4/22/15 11 (16%) Administratively closed to enable activation of new non-match study. S1400B PI3K Total: 39 taselisib: 31 Docetaxel: 8 8%/9% 12/12/16 Docetaxel arm closed: 12/18/15 1 (4%) Closed at interim futility analysis. S1400C (CCGA+) Total: 54 Palbociclib: 37 Docetaxel: 17 19%/15% 09/01/16 Docetaxel arm closed: 12/18/15 2 (6%) Closed at interim futility analysis. S1400D (FGFR+) Total: 45 AZD4547: 35 Docetaxel: 10 16%/12% 10/31/16 Docetaxel arm closed: 12/18/15 2 (7%) Closed at interim futility analysis. S1400E (MET+) Total: 9 R+E: 4 E: 5 N/A (closed too early) 11/26/2014 N/A Closed d/t discontinuation of development of rilotumumab
Conclusion:
Lung-MAP as a master genomic screening protocol has demonstrated feasibility with respect to accrual and evaluation of targeted therapies in lower prevalence patient populations. This dynamic, centralized, single-IRB platform is well positioned to efficiently assess multiple novel therapeutics for advanced SqCCA patients.
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OA 17 - Immunotherapy II (ID 683)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yuichiro Ohe, Anne Tsao
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 301 + 302
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OA 17.08 - Phase II Study of Pembrolizumab for Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Following Completion of Locally Ablative Therapy (LAT) (ID 9449)
15:45 - 15:55 | Author(s): C. Aggarwal
- Abstract
- Presentation
Background:
Patients (pts) with oligometastatic NSCLC may benefit from LAT (e.g., surgery, stereotactic radiation (SRT)). It is unclear if systemic therapy can provide additional benefit after LAT. We are running a Phase II study to evaluate the efficacy of pembrolizumab after LAT, hypothesizing that immunotherapy will be effective in the setting of a minimal disease burden.
Method:
Eligibility stipulates oligometastatic NSCLC (up to 4 sites) with completion of LAT to all known sites of disease. Within 4-12 weeks of completing LAT, pts begin pembrolizumab 200 mg every 21 days for 6 mos, with a provision to continue for a full year in the absence of progression or toxicity. Progression free survival (PFS) and overall survival (OS) are measured from the start of LAT. A sample size of 42 pts provides 80% power for a test at 5% 1-sided type I error to increase PFS to >=10 mos compared to a historical control PFS of 6.6 mo.
Result:
Since January 2015, 39 pts have been enrolled. The median age is 64 years; 54% are male; 90% Caucasian. Current and former smokers comprise 90% of the cohort, with a median of 32 pack yrs. Most common metastatic sites are lung (15 pts), brain (13), and bone (8). LAT has included surgery (24 pts), SRT (23), and concurrent chemoradiotherapy (17). Attributable adverse events (AEs) have been mostly mild and self-limited. There has been one episode of Grade 3 pneumonitis and one episode of Grade 3 adrenal insufficiency. Median follow-up from start of LAT is 16 mos. To date, 11 pts have had progression or death. The median PFS has not yet been reached. The PFS rates (+ SE) at 6, 12 and 18 mos are 92%+5%, 64%+9% and 64%+9%, with 16 and 5 pts at risk beyond 12 and 24 mos, respectively. To date, 8 pts (21%) have died. The median OS has not yet been reached. The OS rates (+ SE) at 6, 12 and 18 mos are 100%, 90%+6% and 75%+9%, with 22 and 5 pts at risk beyond 12 and 24 mos, respectively.
Conclusion:
Use of pembrolizumab after LAT for oligometastatic NSCLC is feasible and well tolerated. In a preliminary analysis, PFS appears favorable. Continued follow-up is necessary to confirm these findings. It is expected that accrual will be complete as of September 2017. Updated survival estimates will be presented.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-059 - Phase I Trial of Gene Mediated Cytotoxic Immunotherapy (GMCI) for Malignant Pleural Effusion (MPE) and Malignant Pleural Mesothelioma (MPM) (ID 10269)
09:30 - 09:30 | Author(s): C. Aggarwal
- Abstract
Background:
GMCI is a tumor-specific immune-stimulator through local delivery of aglatimagene besadenovec, an adenovirus-based vector expressing the HSV-1 thymidine kinase gene (AdV-tk) followed by anti-herpetic prodrug. We conducted a phase I dose escalation trial of intrapleural administration of aglatimagene besadenovec followed by standard chemotherapy in patients with MPE.
Method:
The primary end-point of this dose escalation trial was safety. Eligibility included patients with MPE or MPM with a clinical indication for placement of pleural catheter, age > 18 yrs, ECOG PS 0-1, FEV1> 40% predicted and adequate end organ function. Intra-pleural (IP) AdV-tk was administered at doses of 1x 10[12 ]viral particles (vp) (Cohort 1); 1x10[13 ]vp (Cohort 2); and 1x10[13 ]vp plus celecoxib (Cohort 3). Three patients were treated per cohort with 10 patients in the expansion phase. Valacyclovir (2 gm PO TID x 14 days) started the day after AdV-tk followed by chemotherapy. Secondary end-points included response rate, progression free survival, overall survival and immune response.
Result:
From 2013 to 2015, 19 patients were enrolled and completed therapy: median age 69.5 years (range 41-89), 14 malignant mesothelioma (MM) (9 epithelioid, 3 sarcomatoid, 2 biphasic), 4 non-small cell lung cancer (NSCLC) and 1 breast cancer. Eight patients received IP AdV-tk upon diagnosis, 7 prior to 2[nd] line and 4 prior to 3[rd] line chemotherapy. Safety results have previously been reported. Response according to RECIST was evaluable for 17 pts. Best response was PR in 4 patients (3 with MM, and one pt with NSCLC), 9 SD and 4 PD. As of 05/2017, three patients are alive and in active follow up (one with NSCLC, and 2 with MM), range of follow up 21-32 months. Of the 4 patients with NSCLC, 3 had prolonged disease stabilization (median overall survival 25.7 months post-GMCI), and one patient is still alive 3.6 years from initial diagnosis (29 month post-GMCI).
Conclusion:
We previously reported that GMCI can be safely administered at high-doses IP in combination with chemotherapy. With median follow up of 31 months, we report that the majority of the patients experienced clinical benefit and sustained disease stabilization was seen in patients with NSCLC. Three patients are still alive and in active follow up. Phase II studies are warranted to further determine efficacy based on these preliminary encouraging observations; NCT01997190.
