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Zeshaan Rasheed
Author of
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- 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): Zeshaan Rasheed
- 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
