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Teresa Improta
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-05 - MAGELLAN: Phase 1B Study of Durvalumab with Novel Oncology Therapies, With/Without Chemotherapy, in Untreated Stage IV NSCLC (ID 194)
10:15 - 18:15 | Author(s): Teresa Improta
- Abstract
Background
Immunotherapy with anti-PD-1/PD-L1 antibodies, with or without chemotherapy, is the standard of care in the first-line (1L) treatment for metastatic NSCLC. Despite advances, patients treated with anti-PD-1 directed regimens in metastatic NSCLC have demonstrated median PFS of <1 year. Targeting novel mechanisms in the tumor may improve response rates and survival. For example, danvatirsen is an antisense oligonucleotide that downregulates STAT3, a master regulator of immune suppression, and oleclumab is an anti-CD73 monoclonal antibody that alleviates adenosine-mediated immunosuppression. MAGELLAN is a Phase 1B, open-label, multicenter, biomarker-enriched, multicohort study (NCT03819465), designed to assess the safety and efficacy of durvalumab in combination with novel oncology therapies (danvatirsen, oleclumab), with or without chemotherapy, as 1L treatment for patients with Stage IV NSCLC. Additional novel therapies will be added to this study as supportive preclinical/clinical datasets emerge.
Method
Adult patients with Stage IV NSCLC (histologically/cytologically documented), tumors lacking activating EGFR mutations and ALK rearrangements, WHO/ECOG PS 0–1, and no prior chemotherapy or systemic therapy for Stage IV NSCLC are eligible. Eligible patients will be assigned to the PD-L1 tumor cell (TC) ≥50% or PD-L1 TC<50% cohorts, as confirmed by the VENTANA PD-L1 (SP263) Assay. Immunohistochemical staining with the SP263 assay is concordant with that for the 22C3 assay, another PD-L1 diagnostic assay. Patients in the PD-L1 TC≥50% cohort will be assigned to durvalumab monotherapy (1500 mg q4w), durvalumab+danvatirsen, or durvalumab+oleclumab. Patients in the PD-L1 TC<50% cohort will be assigned to durvalumab+chemotherapy (1500 mg durvalumab q3w up to 4 cycles [+chemotherapy], then q4w [–chemotherapy]), durvalumab+chemotherapy+danvatirsen, or durvalumab+chemotherapy+oleclumab. All therapy will be administered intravenously until disease progression. Oleclumab (1500 mg starting dose) and danvatirsen (200 mg starting dose) in combination with durvalumab or durvalumab+chemotherapy will be administered using a rolling 6-patient design to evaluate for toxicity. The chemotherapy backbone for use with immunotherapy, per investigator’s choice, will be nab‑paclitaxel+carboplatin for squamous and non-squamous NSCLC, gemcitabine+cisplatin/carboplatin for squamous NSCLC, and pemetrexed+carboplatin/cisplatin for non-squamous NSCLC. Patients receiving pemetrexed+carboplatin/cisplatin who do not progress after 4 cycles of chemotherapy will receive pemetrexed maintenance therapy and immunotherapy, unless contraindicated. The primary endpoint is safety and tolerability. Secondary endpoints are objective response rate and PFS (both RECIST v1.1), duration of response, OS, and pharmacokinetics and immunogenicity of durvalumab, oleclumab, and danvatirsen. Identification of candidate biomarkers from blood and tissue samples that may correlate the likely clinical benefit with the treatments under investigation will also be explored. Enrollment is ongoing.
Result
Section not applicable
Conclusion
Section not applicable
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P2.01-18 - ORION: A Phase 2, Randomised, Multicentre, Double-Blind Study to Assess Efficacy and Safety of Durvalumab+Olaparib Versus Durvalumab Alone as Maintenance Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 636)
10:15 - 18:15 | Presenting Author(s): Teresa Improta
- Abstract
Background
Systemic chemotherapy for first-line (1L) metastatic NSCLC shows mixed outcomes. Results from studies using immunotherapy alone or combined with chemotherapy as 1L treatment in patients (pts) with metastatic NSCLC represent a substantial advance, but further improvement is needed. Increased deoxyribonucleic acid damage triggered by polyadenosine 5’diphosphoribose polymerase inhibition may confer antitumour activity, modify tumour immunogenicity and further sensitise tumours to immune checkpoint inhibition, thus promoting a more durable antitumour response. This Phase 2, randomised, multicentre, double-blind study (NCT03775486) is designed to assess the efficacy and safety of durvalumab+olaparib versus durvalumab alone as maintenance therapy in pts whose stage IV NSCLC has not progressed following 1L platinum-based chemotherapy+durvalumab.
Method
Adult pts with stage IV NSCLC with tumours lacking activating EGFR mutations and ALK fusions are eligible. In the initial therapy phase, all pts will receive durvalumab (1500 mg intravenously [IV]) concurrent with platinum-based doublet therapy. Durvalumab+chemotherapy will be administered for 4 cycles for both squamous NSCLC (nanoparticle albumin-bound [nab]-paclitaxel+carboplatin or gemcitabine+carboplatin/cisplatin) and nonsquamous NSCLC (nab-paclitaxel+carboplatin or pemetrexed+carboplatin/cisplatin). Pts whose disease does not progress (complete or partial response [CR/PR] or stable disease [SD]; investigator-assessed RECIST 1.1) will be randomised (1:1) to durvalumab (1500 mg IV, every 4 weeks) + either olaparib (300 mg, oral, twice daily) or its matching placebo until disease progression. Randomisation will be stratified based on objective response to durvalumab+chemotherapy (CR/PR or SD) during the initial therapy phase and histology (squamous or nonsquamous).
Result
The primary endpoint is progression-free survival (PFS) (investigator-assessed, RECIST 1.1). Secondary endpoints are overall survival, PFS in pts with homologous recombination repair-related gene mutation, objective response rate, duration of response, health-related quality of life, pharmacokinetics and immunogenicity of durvalumab, as well as safety.
Conclusion
The study start date was 21 December 2018 and patient enrolment is ongoing. All patients will be followed for survival until the end of the study. The estimated primary completion date is 5 October 2020 and the estimated study completion date is 2 June 2022.
