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Santiago Ponce Aix
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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): Santiago Ponce Aix
- 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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MA13 - Going Back to the Roots! (ID 139)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Maurice Perol, Kaoru Kubota
- Coordinates: 9/09/2019, 14:00 - 15:30, Vancouver (2003)
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MA13.05 - Nab-Paclitaxel Maintenance in Squamous Non-Small Cell Lung Cancer (NSCLC): Updated Results of the Phase III ABOUND.sqm Study (Now Available) (ID 294)
14:00 - 15:30 | Author(s): Santiago Ponce Aix
- Abstract
- Presentation
Background
Background: nab-Paclitaxel maintenance therapy after nab-paclitaxel/carboplatin induction in patients with advanced squamous NSCLC was evaluated in the phase III, randomized, controlled, open-label, multicenter ABOUND.sqm trial. At the 12-month follow-up, there was no statistically significant difference in progression-free survival (PFS) between patients randomized to maintenance nab-paclitaxel + best supportive care (BSC) vs BSC alone. However, a trend of an overall survival (OS) advantage was observed with nab-paclitaxel + BSC vs BSC alone. Here we report the 18-month follow-up of OS.
Method
Methods: Patients (aged ≥ 18 years) with histologically or cytologically confirmed stage IIIB/IV squamous NSCLC and no prior chemotherapy were eligible. Patients received four 21-day cycles of nab-paclitaxel 100 mg/m2 (days 1, 8, and 15) plus carboplatin AUC 6 (day 1) as induction. Patients with radiologically assessed complete or partial response or stable disease without clinical progression after 4 cycles were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 of each 21-day cycle) plus BSC or BSC alone until disease progression. The primary efficacy analysis was performed on the ITT population. PFS from randomization into the maintenance part of the study was the primary endpoint. Secondary endpoints included safety, OS (from randomization), and response.
Result
Results: 420 patients received induction therapy; 202 were randomized to maintenance nab-paclitaxel + BSC (n = 136) or BSC alone (n = 66). The median PFS in patients in the nab-paclitaxel + BSC arm vs those in the BSC-alone arm was 3.1 vs 2.6 months (HR, 0.85; P = 0.349), respectively; the median OS was 17.8 vs 12.2 months (HR, 0.71; P = 0.058), respectively. The overall response rate was 69.1% vs 57.6% (RRR, 1.20; P = 0.087). Following the maintenance part, 73.5% (nab-paclitaxel + BSC) and 68.2% (BSC alone) of patients received subsequent anti-cancer treatment. Over the entire study, the most frequent grade 3/4 TEAEs were neutropenia (53.1% vs 50.0%) and anemia (33.1% vs 32.3%); only peripheral neuropathy occurred in ≥ 5% of patients during maintenance (13.1% in the nab-paclitaxel + BSC arm).
Conclusion
Conclusion: Although PFS and OS differences were not statistically significant in the ITT population, the 18-month follow-up of OS demonstrated the feasibility of nab-paclitaxel maintenance therapy for patients with anced squamous NSCLC.
ClinicalTrials.gov identifier: NCT02027428
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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): Santiago Ponce Aix
- 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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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-01 - RELAY EU/US Subset: Ramucirumab Plus Erlotinib Improves Progression-Free Survival in First-Line EGFR Mutation-Positive NSCLC (Now Available) (ID 356)
09:45 - 18:00 | Presenting Author(s): Santiago Ponce Aix
- Abstract
Background
Dual blockade of EGFR and VEGFR pathways in EGFR mutation-positive NSCLC augments anti-tumor efficacy versus EGFR inhibition alone. The RELAY (NCT02411448) phase 3 study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for erlotinib plus ramucirumab versus erlotinib plus placebo in patients with previously untreated EGFR mutation-positive metastatic NSCLC (median PFS 19.4 vs 12.4mo, HR 0.591 (95% CI 0.461–0.760), p<0.0001). Here we report efficacy and safety data of the EU/US subset.
Method
Eligible patients (untreated, metastatic NSCLC with an EGFR exon 19 deletion or exon 21 (L858R) substitution mutation and no CNS metastasis) were randomized (1:1) to receive 150 mg daily oral erlotinib plus 10 mg/kg intravenous ramucirumab (RAM+ERL) or placebo (PL+ERL) Q2W until progressive disease or unacceptable toxicity. Patients were stratified by geographic region (East Asia vs ‘other’, i.e. EU/US). Primary endpoint was investigator-assessed PFS. Other key objectives included safety, ORR, DoR, PFS2, and OS.
Result
In the EU/US, 113 (25.2%) of 449 total patients (58 RAM+ERL, 55 PL+ERL) were randomized between Feb 2016-Feb 2018. Baseline characteristics were balanced between treatment arms: ~60% female, ~52% never-smokers and ~66% Ex19del. RAM+ERL improved PFS and had a longer DoR (Table). PFS2 and OS data were immature. Grade≥3 TEAEs occurring in >5% of patients included (RAM+ERL vs PL+ERL): hypertension (29.8% vs 7.3%), diarrhea (12.3% vs 1.8%), AST increased (7.0% vs 3.6%), ALT increased (7.0% vs 1.8%), dermatitis acneiform (5.3% vs 9.1%), fatigue (5.3% vs 0%), and rash (0% vs 5.5%).
Abbreviations: CI=confidence interval; DoR=duration of response; ERL=erlotinib; HR=hazard ratio; N=total population; n=total responders; NR=no response; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PL=placebo; RAM=ramucirumab RAM + ERL (N=58) PL + ERL (N=55) Unstratified HR (95% CI) p-value PFS Median, months (95% CI) 20.6 (14.7-26.0) 10.9 (8.3-19.4) 0.605 (0.362-1.010) 0.0523 Censoring rate
52% 38% ORR, % (95% CI)
74.1 (62.9-85.4) 76.4 (65.1-87.6) NA 0.8319 DoR, for responders only n=43 n=42 Median, months (95% CI) 18.0 (12.7-22.0) 10.0 (7.1-17.7) 0.527 (0.296-0.939) 0.0274 Censoring rate
54% 33% PFS2 Median, months (95% CI) NR NR 0.632 (0.304-1.313) 0.2143 Censoring rate 79% 67% OS Median, months (95% CI) NR NR 1.096 (0.465-2.582) 0.8344 Censoring rate 81% 82%
Conclusion
The EU/US subset analysis was consistent with the full ITT population where RAM+ERL demonstrated a statistically significant improvement in PFS over PL+ERL. Efficacy and tolerability were similar to that of the overall RELAY study population. Ramucirumab is an effective and safe addition to standard-of-care EGFR-TKI for treating EGFR mutation-positive metastatic NSCLC.
