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Jose Manuel Trigo Perez
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-28 - Real World Use of Afatinib in NSCLC EGFRm+ Patients Outside Clinical Trials: A FAETT Experience (Now Available) (ID 655)
08:00 - 18:00 | Author(s): Jose Manuel Trigo Perez
- Abstract
Background
Epidermal growth factor receptor (EGFR) tyrosine kynase inhibitors (TKIs) remain the standard of care as first-line therapy for patients with non-small cell lung cancer (NSCLC) harboring an EGFR mutation. These drugs have been associated with improvements in both clinical outcomes and tolerability, compared with platinum-based chemotherapy.
Three generations of TKIs are currently approved in the first-line setting, though only first (erlotinib and gefitinib) and second generation blockers (mainly afatinib, but also dacomitinib) have been extensively used in clinical practice nowadays.
Method
We reviewed 105 patients with NSCLC with advanced or recurrent stages that harbour EGFR mutations, treated with afatinib as first´line therapy among the academic hospitals adhered to the FAETT network.
Result
The information of clinical, pathological and treatment characteristics of the patients was collected retrospectively and the statistical analysis was performed with the software SPSS software version 21.0, considering the statistical significance if p-value <0.05.
The characteristics of the patients are reflected in Table 1.
The mean age at the beginning of treatment with afatinib was 61 (37-81) years. 48.6% of the patients were older than 65 years. 27.6% were older than 70 years. With a median follow-up of 15 months (0-82), the median progression-free survival was 14 months (10.74-17.26) Fig 1, and the median overall survival was 31 months (24.00) -37.99).
The median PFS and OS among patients older than 65 years, and even those older than 70 years, is not statistically significant (14 vs 13 and 30 vs 31 months, repectively. P-value:0,83 and 0,78
On the other hand, the toxicities between both groups remain similar, with diarrhea and skin rash standing out as the most frequent, as reflected in the data published to date. Table 2
Conclusion
This retrospective study shows no differences in the use of afatinib among older patients in terms of both efficacy and tolerability.
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.06 - Efficacy Results of Selective AXL Inhibitor Bemcentinib with Pembrolizumab Following Chemotherapy in Patients with NSCLC (Now Available) (ID 2271)
10:30 - 12:00 | Author(s): Jose Manuel Trigo Perez
- Abstract
- Presentation
Background
The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.
Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.
Method
This phase II trial (Cohort A, NCT03184571) enrolled 48 advanced lung adenocarcinoma patients with progression on or after no more than one prior line of platinum-based chemotherapy. Patients with EGFR/ALK mutations were included in this study and must have progressed on or after at least one standard targeted therapy. The primary endpoint was ORR according to RECIST v1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS, and safety. Tumour biopsies were analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.
Result
As of April 2019, the trial was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers.
At time of writing, a total of 210 treatment cycles had been completed by all patients. 17 patients were ongoing.
17 of 32 biomarker-evaluable patients (53%) were PD-L1 negative, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Of 28 biomarker-evaluable patients, 14 (50%) expressed AXL on their tumours.
Among patients who had at least 1 evaluable on-treatment scan: 5 responses were observed in 13 AXL positive patients (38%), and 7 in 30 patients with TPS 0-49% (23%). There were 10 responses observed among 34 evaluable patients overall (29%).
In Stage 1, two of the 4 AXL positive responses are ongoing; mDoR is not mature in the AXL positive patients. mPFS was 5.9 mo in AXL positive patients (n=10, 3.0-NR) and 4.0 mo (95% CI 1.9-NR) overall (n=24). mOS was not mature.
The most common TRAEs (occurring in >10% of patient in both stages) were transaminase increases (34%), asthenia/fatigue (30%), diarrhoea (26%), nausea (13%), anaemia (11%), decreased appetite (11%), and pruritus (11%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments.
Conclusion
Patients had predominantly low or no PD-L1 expression; approximately half were AXL positive. The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients, particularly in those with AXL positive disease, including PD-L1 negative patients. Mature ORR for both stages, as well as 12-month OS for stage 1 will be presented at the meeting.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-72 - A Phase II Study of Selective AXL Inhibitor Bemcentinib and Pembrolizumab in Patients with NSCLC Refractory to Anti-PD(L)1 (ID 1632)
09:45 - 18:00 | Author(s): Jose Manuel Trigo Perez
- Abstract
Background
The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.
Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.
The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients (Cohort A, NCT03184571), particularly in those with AXL positive disease, including PD-L1 negative patients.
The novel combination is now being assessed in patients refractory to anti-PD-(L)1 therapy, considering the emerging need in this population and AXL’s role as a mediator of resistance.
Method
This is an open-label, single-arm, 2-stage phase II study (Cohort B, NCT03184571) to evaluate the safety and efficacy of bemcentinib (200mg/d) in combination with pembrolizumab (200mg/q3wk) in patients post anti-PD-(L)1 therapy. The primary endpoint is overall response rate (ORR), and additional endpoints include efficacy by biomarker expression, duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. Clinical efficacy endpoints are based on tumour imaging evaluable by RECIST v1.1.
Eligible patients received a maximum of 2 prior lines of therapy, with the most recent course having included a PD-(L)1 inhibitor. To be eligible, patients must have exhibited disease control (CR/PR/SD) for at least 6 months on prior PD-(L)1 inhibitor therapy with disease progression occurring within 12 weeks since last dose.
Bemcentinib will be administered as a loading dose of 400mg on days 1, 2 and 3 followed by a dose of 200mg once daily. A fixed dose of 200 mg pembrolizumab will be given by intravenous infusion over 30 minutes every 3 weeks. Bemcentinib and pembrolizumab will be given until disease progression, unacceptable dose toxicity, or for a maximum of 35 cycles.
Tumour specimens will be analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.
The pre-specified efficacy threshold for continuation into the second stage is 1 objective response among the first 13 patients, at which point up to a further 16 patients may be evaluated, for a total of 29 patients.
Result
Section not applicable
Conclusion
Section not applicable
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-03 - Antitumor Activity of Single Agent Lurbinectedin in Patients with Relapsed SCLC Occurring ≥30 Days After Last Platinum Dose (ID 1710)
09:45 - 18:00 | Presenting Author(s): Jose Manuel Trigo Perez
- Abstract
Background
Lurbinectedin (L) inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis.
Method
This multicenter, single agent, phase II Basket trial treated a cohort of 105 SCLC patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line. L 3.2 mg/m2 was administered as a 1-hour i.v. infusion on Day 1 q3wk. Primary endpoint, confirmed overall response rate (ORR) by RECIST v.1.1 according to investigator assessment, was met (ORR=35.2%; 95% CI, 26.2-45.2%). A sub-analysis excluding the 21 pts with disease relapse < 30 days after last platinum dose is reported here.
Result
Median age of 84 evaluated pts was 60 years (range, 41-83), 58.3% were male, ECOG PS 0-1/2 in 96/4%, liver metastasis in 36.9%, history of CNS involvement in 4.8%, prior platinum in 100%, median chemotherapy-free interval (CTFI)=3.9 months (1.1-16.1); prior immunotherapy in 8.3%. A median of 5.5 cycles (range, 1-24) was administered.
ORR, % (95% CI) (confirmed responses) (n=84)
40.5 (29.9-51.7)*
CTFI≥90d (n=60)
45.0 (32.1-58.4)
CTFI 30-89d (n=24)
29.2 (12.6-51.1)
Disease Control Rate at 6 months, % (n=84)
48.8
Median duration of response (months) (95% CI) (n=34)
5.3 (3.5-6.4)
CTFI≥90d (n=27)
6.2 (3.5-7.3)
CTFI 30-89d (n=7)
4.1 (2.6-5.3)
Median overall survival (months) (95% CI) (n=84)**
10.9 (7.8-14.9)
CTFI≥90d (n=60)**
11.9 (9.7-16.2)
CTFI 30-89d (n=24)**
(4.1-7.6)
*4 of 7 pts who failed prior immunotherapy had confirmed response
**Preliminary data
L was well tolerated. Neutropenia was the most common adverse event (AE) (G3:21.5% and G4:25%), whereas febrile neutropenia was reported in 2.4%. Most common non-hematological AEs included fatigue (G3: 7.1%), nausea and vomiting (all G1-2: 32.1% and 16.7%) and transaminase increase (G3:7.2%). There was no death due to treatment related AE.
Conclusion
L is an active agent for second-line treatment of SCLC. The highest ORR (45.0%) was reported for pts with CTFI≥90d. Notable antitumor activity (ORR=29.2%) was also observed in pts with CTFI 30-89d, for whom no therapy is currently approved. Hence, L is a valuable therapeutic option for SCLC pts with disease relapse after first-line platinum-based therapy.
Updated trial results will be presented at the conference.
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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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P2.01-12 - A Phase I/II Trial of IO102 and Pembrolizumab With/Without Chemotherapy as First-line Treatment of Metastatic NSCLC (ID 706)
10:15 - 18:15 | Author(s): Jose Manuel Trigo Perez
- Abstract
Background
Immunotherapy has significantly changed the treatment landscape of non-small cell lung cancer (NSCLC) with no driver mutations. However, despite the addition of anti-PD-1/PD-L1 therapies to the clinical armamentarium only a subset of patients derives durable benefit. IO102 is a novel, second generation, HLA-A unrestricted immune modulating T-win® vaccine targeting IDO. IO102 has a dual mode of action; remodulation of the tumour micro-environment through elimination of immune suppressive cells, and induction of CD8 T-cell mediated killing of IDO-expressing tumor cells. Our first-generation IDO vaccine (IO101) has shown promising antitumor activity and a favorable safety in heavily pretreated NSCLC patients (Iversen, CCR 2013).
Method
Phase I/II, international, multicenter, open-label, randomized trial with two parallel cohorts. Cohort A: IO102 (100µg s.c.) and pembrolizumab (200 mg) (PD-L1 ≥ 50%); Cohort B: IO102, pembrolizumab and carboplatin plus pemetrexed (PD-L1 < 50%). The maximum treatment duration is 35 cycles (app. 2 years). Key eligibility criteria include metastatic NSCLC or non-squamous NSCLC (cohort B) with no prior treatment for metastatic NSCLC and no driver mutations.
Phase I is a non-randomized safety run-in with 6 patients per cohort investigating one dose level of the experimental arms. Only one DLT is allowed in each cohort. Phase II is following Sargent’s two-stage, three-outcome optimum design (Sargent, ClinTrial2001) with a 2:1 randomization in the cohorts. Cohort A: IO102 and pembrolizumab versus pembrolizumab alone; Cohort B: IO102, pembrolizumab and chemotherapy vs. pembrolizumab and chemotherapy. Provision of blood and tumour tissue is required for biomarker studies.
The primary endpoint is safety and objective response rate (ORR) per RECIST 1.1 in Phases I and II, respectively. Secondary endpoints include ORR per iRECIST, duration of response, progression free survival, overall survival, and biomarkers including immunoscore in tissue, tumour mutational burden and immunomonitoring in blood.
The study is enrolling in Europe. First patient was entered in September 2018 and recruitment is expected to continue throughout 2019: EudraCT Number 2018-000139-28 / IND Number: 018081.
Result
Section not applicable
Conclusion
Section not applicable
