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Tawee T Tanvetyanon
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OA05 - Clinical Trials in IO (ID 899)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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OA05.03 - Safety and Clinical Activity of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes (TIL) Combined with Nivolumab in NSCLC (ID 14388)
13:50 - 14:00 | Author(s): Tawee T Tanvetyanon
- Abstract
- Presentation
Background
Adoptive transfer of tumor infiltrating lymphocytes (TIL) can cause durable regression by recognition of neoantigens unique to the patient. NSCLC TIL has synergistic preclinical activity with nivolumab, and we hypothesized it may induce remissions in anti-PD1-refractory patients. We initiated a phase I trial with the primary objective to characterize the safety and preliminary activity of the combination.
a9ded1e5ce5d75814730bb4caaf49419 Method
Metastases from patients with Stage 4 NSCLC were resected, morselized, cultured, and tested for autologous reactivity. Reactive TIL fragments were pooled and cryopreserved. Patients received nivolumab over 8 weeks. Patients with progressive disease (PD) proceeded to lymphodepletion cyclophosphamide/fludarabine (Cy/Flu), TIL, and IL-2. Tumor whole exome sequencing, transcriptomics, and LC-MS/MS peptide sequencing was performed. TCR-Vß rearrangements were analyzed from tumor, TIL, and pre-/post-infusion peripheral lymphocytes.
4c3880bb027f159e801041b1021e88e8 Result
Of 14 patients enrolled to date, 13 had successful ex vivo TIL expansion from resected metastases. TIL had high proliferative capacity, expanding to median 81 billion CD3+ cells infused per patient (range 27–138 billion) and median 27% of fragments were autologously reactive (range 0-67%). Demographics: median age 54 (range 44-74), median TMB 4 mutations/MB (range 0.9–25), median PD-L1 proportion-score 0% (range 0–100%), and 4 had LKB1 allelic inactivation. Predicted neoantigens correlated with variants on proteomic sequencing. Outcomes: 9 patients had confirmed PD on nivolumab, and proceeded to receive Cy/Flu/TIL/IL-2. No unexpected serious adverse reactions (SUSARs) were identified. Of these 9 patients, 7 had reduction in sum of target lesions at Day+28 CT scan (Figure 1). Peripheral lymphocytes expanded at Days 2-7 in the majority of patients. In patients tested to date, TIL clonotypes persisted through Day+100, and CCR7+CD95+CD45RA+ stem cell-like memory (TSCM) cells were increased at post-infusion timepoints.
8eea62084ca7e541d918e823422bd82e Conclusion
Adoptive cell transfer with TIL and nivolumab for NSCLC had acceptable toxicity and preliminary activity in this ongoing trial.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-32 - Phase I/II Study of the A2AR Antagonist NIR178 (PBF-509), an Oral Immunotherapy, in Patients (pts) with Advanced NSCLC (ID 12495)
16:45 - 18:00 | Author(s): Tawee T Tanvetyanon
- Abstract
Background
Background: ATP is catabolized to adenosine in the tumor microenvironment, leading to excess adenosine and immunosuppressive effects via immune checkpoint protein adenosine 2A receptor (A2AR). NIR178 is an oral A2AR antagonist that selectively binds and inhibits A2AR, reactivating T cell-mediated antitumor immune response. This Phase I/II study evaluated NIR178 in previously treated pts with advanced NSCLC (NCT02403193).
a9ded1e5ce5d75814730bb4caaf49419 Method
Methods: Pts (ECOG PS 0─1) had received ≥1 prior line of therapy; EGFR/ALK pts had failed prior TKI therapy. Objectives: primary – determine MTD of single-agent NIR178; secondary – efficacy endpoints, PK, and evaluation of PD-L1 expression.
4c3880bb027f159e801041b1021e88e8 Result
Results: At 13 Dec 2017 data cut-off, 24 pts had been treated: median age 68 yrs, 46% male; 79% received prior immunotherapy; 22/24 (92%) pts had discontinued (due to progression [n=13], death [n=2], AEs [n=2] or other reasons [n=5]) and 2/24 (8%) pts remained on treatment. Dose levels evaluated: 80 (n=3), 160 (n=3), 320 (n=7), 480 (n=6), 640 mg BID (n=5). There was 1 DLT: Gr 3 nausea (640 mg). The most frequent (≥20%) any-Gr AEs regardless of causality were nausea (67%), fatigue (63%), dyspnea (46%), vomiting (33%), chest pain and other (29%), gastroesophageal reflux disease, anemia, diarrhea (all 25%), anorexia, back pain, generalized muscle weakness and cough (all 21%). Drug-related Gr 3 AEs were pneumonitis (8%) and nausea (4%); no Gr 4 AEs were reported. Potential immune-related any-Gr AEs were rash (8%), pneumonitis (8%), hypothyroidism, increased ALT/AST (all 4%). NIR178 systemic exposure (Cmax, AUC) increased more than proportionally with dose. Efficacy data for 17/24 treated pts demonstrated responses and SD across the dose range, including 1 confirmed CR (480 mg) and 1 PR (80 mg), both in immunotherapy-naïve pts. Durable SD >44 wks with tumor shrinkage was observed in 2 ongoing immunotherapy-exposed pts. Disease control was seen in pts with both high and low baseline PD-L1 expression.
8eea62084ca7e541d918e823422bd82e Conclusion
Conclusions: NIR178 was well tolerated; AEs were manageable and there were no Gr 4 drug-related AEs. Immune-related AEs may indicate immune stimulation. Clinical benefit was observed in immunotherapy-exposed and -naïve pts irrespective of PD-L1 status.
6f8b794f3246b0c1e1780bb4d4d5dc53
