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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
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)
11:00 - 12:30 | Author(s): Lyudmila Bazhenova
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.
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.
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
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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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.03-044 - Exploratory Analysis of Lung Cancer Patients in a Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) plus Gemcitabine (ID 10174)
09:30 - 16:00 | Presenting Author(s): Lyudmila Bazhenova
NC-6004 is a polymeric micelle exhibiting sustained release of cisplatin and selective distribution to tumors, reducing plasma C~max~ and increasing AUC. Preclinical data showed less neuro- and nephrotoxicity with greater anti-tumor activity versus cisplatin. A previous trial evaluated NC-6004 and gemcitabine defining a recommended phase 2 dose of 90 mg/m. A Bayesian continual reassessment method (N-CRM) design evaluated escalating doses of NC-6004 in combination with gemcitabine at 1250 mg/m.
Patients with refractory solid tumors were enrolled at four US sites. NC-6004 was administered intravenously (IV) at 60-180 mg/m over 1 hour on Day 1 with gemcitabine at 1250 mg/m IV over 30 mins on Day 1 and Day 8 every 3 weeks. All patients were administered a hydration regimen. Escalation of NC-6004 began with a single patient run-in, escalating by 15 mg/m until a dose limiting toxicity (DLT) occurred at 180 mg/m. Cohorts of four patients were then enrolled at each dose predicted by the N-CRM design. The maximum tolerated dose (MTD) was defined as the dose with the greatest posterior probability of target toxicity < 25%.
Among 22 patients enrolled in Phase 1b, 11 patients (six male, five female) had lung cancer. Non-squamous non-small cell lung cancer (NSCLC) was the most common subtype in 8/11 (72%) followed by squamous NSCLC, SCLC and large cell neuroendocrine histology in 1/11 (9%) of each type. Patients received a mean of 1.7 (range, 1-5) prior lines of therapy with 82% receiving a prior platinum agent. Common Grade 3/4 hematologic adverse events (AEs) among all patients were leukopenia (27%), thrombocytopenia (27%), anemia (18%) and neutropenia (18%). All AEs/DLTs were manageable and resolved. Of the four lung cancer patients treated at the MTD (135 mg/m), the mean number of cycles received was 6 (range, 2-17). The total cumulative doses were 120-2340 mg/m. Of ten patients evaluable, partial response was observed in 2/10 and stable disease in 7/10. Tumor shrinkage was observed in 6/10.
The nanoparticle formulation allowed greater cisplatin equivalent doses with no clinically significant neuro-, oto- or nephrotoxicity allowing patients to receive treatment for a longer duration. Activity was observed in heavily pretreated platinum exposed lung cancer patients with a majority of patients exhibiting tumor regression or stable disease. NC-6004 with gemcitabine demonstrated promising activity and tolerability in heavily pretreated lung cancer patients in this trial and warrants further investigation.