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Reyes Bernabe Caro
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FP10 - Small Cell Lung Cancer/NET (ID 231)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP10.04 - RESILIENT Part 1: Safety and Efficacy of Second-Line Liposomal Irinotecan in Patients with Small Cell Lung Cancer (ID 3657)
00:00 - 00:00 | Author(s): Reyes Bernabe Caro
- Abstract
- Presentation
Introduction
Many patients with small cell lung cancer (SCLC) develop drug resistance to first-line platinum-based chemotherapy, and second-line therapies are limited. RESILIENT (ClinicalTrials.gov identifier NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of liposomal irinotecan monotherapy as second-line treatment for patients with SCLC. Here we report data from part 1 of the RESILIENT study (data cut off, 2 December 2019).
Methods
RESILIENT part 1 was an open-label, single-arm study comprising dose-exploration and dose-expansion phases. Eligible patients with SCLC were aged ≥ 18 years, had progressed with platinum-based first-line therapy, had an Eastern Cooperative Oncology Group performance status score of 0 or 1, and had adequate organ function; prior exposure to immunotherapy was permitted. During dose exploration, participants received liposomal irinotecan 85 mg/m2 or 70 mg/m2 free base administered every 2 weeks; the identified recommended dose was used during dose expansion. Primary endpoints were safety and tolerability. Efficacy assessments included objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), and overall survival (OS).
Results
In total, 30 patients received liposomal irinotecan in RESILIENT part 1 (women, 56.7%; median age, 61.5 years). During dose exploration, four patients who received liposomal irinotecan 85 mg/m2 experienced dose limiting toxicities, including diarrhea (n = 3) and abnormal liver function test (n = 1). Thus, this dose was not considered tolerable and enrollment into the 70 mg/m2 cohort was initiated; a total of 25 patients (platinum resistant, 40%) received liposomal irinotecan 70 mg/m2 (dose exploration, 12 patients; dose expansion, 13 patients). Among the 25 patients who received the recommended dose of 70 mg/m2, 40% had one or more grade ≥ 3 treatment-related treatment-emergent adverse events (TEAEs), most commonly diarrhea (20%), neutropenia (16%), and anemia, thrombocytopenia, asthenia and abdominal sepsis (each 8%); 8% of patients discontinued treatment owing to TEAEs. Median (95% CI) PFS was 3.98 (1.45–4.24) months and OS was 8.08 (5.16–9.82) months. ORR (complete response + partial response) was 44% and BOR was: complete response, 4%; partial response, 40%; stable disease, 28%; progressive disease, 20%; non-evaluable, 8%.Thirty patients were treated in RESILIENT part 1. Full results to be presented in the updated abstract.
Conclusion
In participants with SCLC who had progressed with platinum-based first-line therapy, liposomal irinotecan at the recommended dose of 70 mg/m2 showed promising antitumor activity and safety findings were aligned with the known safety profile. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial versus topotecan will provide further data regarding the efficacy and safety of liposomal irinotecan 70 mg/m2 for the second-line treatment of patients with SCLC.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.14 - RESILIENT Part 2: A phase 3 Study of Liposomal Irinotecan in Patients with Small-Cell Lung Cancer in the Second-Line Setting (ID 3485)
00:00 - 00:00 | Author(s): Reyes Bernabe Caro
- Abstract
Introduction
Small cell lung cancer (SCLC) accounts for approximately 15% of lung cancers. SCLC is usually sensitive to established first-line therapies, but many patients relapse and develop resistance to platinum-based first-line treatment. Currently, the topoisomerase 1 inhibitor topotecan is the only approved second-line therapy for SCLC in the USA and Europe. Liposomal irinotecan is an intravenous formulation that encapsulates the topoisomerase 1 inhibitor irinotecan in a lipid-bilayer vesicle, leading to prolonged circulation. The safety, tolerability and efficacy of liposomal irinotecan monotherapy in patients with SCLC who progressed with platinum-based first-line therapy is being evaluated in RESILIENT (NCT03088813), a two-part phase 2/3 study. Preliminary data from the dose-ranging part of the study (part 1) indicated that liposomal irinotecan 70 mg/m2 (free base equivalent) administered every 2 weeks was well tolerated and had promising antitumour activity.1 Here, we present the design of RESILIENT part 2, which will assess the efficacy and safety of liposomal irinotecan versus topotecan in the same patient population.
References
Paz-Ares L et al. Poster presented at the 2019 American Society of Clinical Oncology conference, May 31–June 4, 2019, Chicago, IL, USA
Methods
RESILIENT part 2 is a phase 3, open-label study with a planned sample size of 450. Participants are randomized 1:1 to intravenous liposomal irinotecan or intravenous topotecan. Liposomal irinotecan is administered at 70 mg/m2 every 2 weeks and topotecan is administered at 1.5 mg/m2 for 5 consecutive days every 3 weeks. A total of 254 patients have been randomized and received treatment to date (as of August 8, 2020). Tumour assessments are performed using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Response Assessment in Neuro-oncology criteria for CNS lesions. Improvements in symptoms are measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the European Organization for Ressearch and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13. Safety assessments include monitoring for adverse events. Overall survival is the primary endpoint of the study. Progression-free survival, objective response rate and proportion of patients reporting symptom improvement are secondary endpoints. Participants will continue study treatment until disease progression, unacceptable toxicity or study withdrawal. Participants will be followed for survival until death or study end, which is when all patients have died, withdrawn consent or are lost to follow-up.
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P77 - Immunotherapy (Phase II/III Trials) - Combining Different Immunotherapeutic Approaches (ID 254)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P77.02 - Efficacy of Tiragolumab + Atezolizumab in PD-L1 IHC and TIGIT Subgroups in the Phase II CITYSCAPE Study in First-Line NSCLC (ID 3501)
00:00 - 00:00 | Author(s): Reyes Bernabe Caro
- Abstract
Introduction
The immunomodulatory receptor TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint on activated T cells and natural killer cells in multiple cancers. Tiragolumab (tira) is a humanized IgG1/kappa monoclonal antibody that binds TIGIT to prevent its interaction with its ligand PVR (CD155). Because PD-L1 expression is considered a hallmark of pre-existing immunity and is positively correlated with TIGIT expression, we investigated the combination of tira + atezolizumab (atezo) in patients with newly diagnosed PD-L1-positive metastatic NSCLC in the phase II CITYSCAPE trial. We recently reported an improvement in progression-free survival (PFS) with the tira + atezo combination over atezo monotherapy in patients whose tumors showed high PD-L1 expression (≥50% TPS or tumor proportion score) by the pharmDx immunohistochemistry (IHC) 22C3 assay (PFS hazard ratio [HR] 0.30, 95% confidence interval [CI]: 0.15-0.61) [Rodriguez-Abreu. ASCO 2020]. To determine whether these results were consistent across different PD-L1 IHC assays, we assessed the efficacy of tira + atezo in PD-L1 subgroups defined by the SP263 IHC assay. We also evaluated whether TIGIT expression was associated with tira + atezo efficacy.
Methods
PD-L1 expression was assessed prospectively using 22C3 IHC and retrospectively with SP263 IHC, both of which yield a tumor cell (TC) membrane staining score. TIGIT expression on tumor-infiltrating immune cells (IC) was assessed with an exploratory IHC assay.
Results
Among the 135 enrolled patients with PD-L1-positive NSCLC (intent-to-treat [ITT] population), 113 had results from the SP263 assay and 105 had results from the TIGIT assay. The biomarker-evaluable populations (BEP) for both of these assays were similar to the ITT population. Comparable PFS improvement with tira + atezo relative to atezo monotherapy was seen in PD-L1–high (≥50% TC) subgroups defined by SP263 (PFS HR 0.23, 95% CI: 0.10–0.53) when compared with PD-L1-high subgroups defined by 22C3. However, for patients whose tumors were defined as TIGIT-high (≥5% IC), no strong association with PFS improvement was observed.
ConclusionBiomarker subgroup
Subgroup, n (BEP, N)
PFS HR (CI) relative to atezo monotherapy arm
ITT (PD-L1 IHC 22C3 >1% TPS)
135 (135)
0.58 (0.39–0.88)
PD-L1 IHC 22C3 (≥50% TPS)
58 (135)
0.30* (0.15–0.61)
PD-L1 IHC SP263 (≥50% TC)
45 (113)
0.23* (0.10–0.53)
TIGIT IHC (≥5% IC)
49 (105)
0.62* (0.30–1.32)
*Unstratified HR
Prevalence of PD-L1 subgroups in the BEP was comparable with previous reports for both IHC assays. The PFS benefit observed with tira + atezo in patients with tumors defined as PD-L1-high by 22C3 was also observed using the SP263 IHC assay, but not in tumors classified as TIGIT-high using an exploratory TIGIT IHC assay. Our results suggest that PD-L1 expression, assessed by 22C3 or SP263, may be a biomarker for tira + atezo combination therapy in metastatic PD-L1-positive untreated NSCLC.
