Virtual Library
Start Your Search
Carlos Arce-Lara
Author of
-
+
P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.04-27 - Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC (ID 14307)
16:45 - 18:00 | Author(s): Carlos Arce-Lara
- Abstract
Background
Bemcentinib (BGB324) is a first-in-class, highly selective oral inhibitor of the AXL tyrosine kinase currently in phase II clinical development across several cancer types. AXL overexpression has been observed in pts failing anti-PD-1 therapy in several cancers whereas AXL inhibition via bemcentinib has shown synergistic effect with checkpoint blockade in pre-clinical models of NSCLC.
In pts with advanced, pre-treated NSCLC, bemcentinib monotherapy led to disease stabilisation in 2 out of 8 pts including evidence of tumour reduction. Combination therapy of bemcentinib with EGFR inhibition indicated the potential of AXL blockade to reverse resistance to targeted therapy in advanced EGFR therapy resistant NSCLC. Evidence of immune activation following bemcentinib monotherapy was observed in AML patients.
This open label, single-arm, two-stage Phase 2 study was designed to test whether AXL inhibition may increase the efficacy of pembrolizumab in patients with advanced, previously treated adenocarcinoma of the lung.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with documented Stage IV adenocarcinoma of the lung who had progressed on previous platinum chemotherapy and – if applicable – at least one line of licensed EGFR or ALK targeted therapy, received 200 mg/d bemcentinib po and 200 mg/q3wk pembrolizumab iv. Patients were required to consent to a fresh pre-treatment biopsy. Tumour assessments were done 9-weekly. The primary endpoint was ORR. Tumour biopsies were analysed for PD-L1 and AXL as well as immune cell populations. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) in patients pre-dose and at C2D1.
4c3880bb027f159e801041b1021e88e8 Result
As of time of writing, the study had fully recruited its first stage. Of 24 patients enrolled, 14 were ongoing. 6 of 10 patients who had reached their first scan showed evidence of tumour shrinkage including 3 pts with partial responses in their target lesions. 2 patients had stable disease. There were no grade 4 treatment-related events. Dose reduction from 200 to 100 mg/d of bemcentinib as a consequence of adverse events was required in 12% of patients. Correlation of AXL and PD-L1 expression with response was evaluated. Soluble AXL plasma levels were increased following one cycle of treatment indicative of target engagement.
8eea62084ca7e541d918e823422bd82e Conclusion
A preliminary analysis of response to combination treatment during the first stage of this study as well as biomarker correlation will be presented at the meeting. Clinical trial information: NCT03184571
6f8b794f3246b0c1e1780bb4d4d5dc53 -
+
P2.04-28 - Use of Immune Checkpoint Inhibitors (ICIs) in Patients with Refractory Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status (PS) (ID 13279)
16:45 - 18:00 | Author(s): Carlos Arce-Lara
- Abstract
Background
Patients with poor PS generally do not tolerate chemotherapy well, and best supportive care is advocated for patients with Eastern Cooperative Oncology Group (ECOG) PS of 3 or greater. However, immune checkpoint inhibitors (ICIs) are generally better tolerated than conventional chemotherapy, making these drugs attractive options for poor PS patients. Scant literature exists on the safety and efficacy of ICIs in patients with poor PS.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively identified patients who received single-agent programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors for refractory NSCLC between January 2015 and December 2017 at our institution. Descriptive tables of patient-, disease-, and treatment-related variables were generated. Overall survival (OS) was stratified by performance status and compared utilizing the Kaplan-Meier method. Multivariable survival analysis was performed using a Cox regression model.
4c3880bb027f159e801041b1021e88e8 Result
In total, 111 patients received PD-1/PD-L1 inhibitors for refractory NSCLC. PS was 0 in 6 (5%) patients, 1 in 53 (48%) patients, 2 in 37 (33%) patients and 3 in 10 (9%) patients, and 5 patients did not have a recorded PS. Median OS was significantly longer in the PS 0-1 group than the PS 2-3 group (11.3 months vs 4.1 months, p=0.02). Poorer PS (ECOG 2-3) was significantly associated with increased risk for death when controlling for confounding variables (HR 2.1, p=0.004).
Specifically, within the PS 3 group, 2 of 10 patients developed objective responses (1 partial response, 1 complete response). Two patients (20%) had progressive disease. Six patients were non-evaluable for response due to death. The median overall survival was 2.6 months, with the two responding patients both alive over 540 days from initial ICI dose. However, 5 of the 10 patients died within 50 days of initial ICI dose. One of the responding patients developed nivolumab-induced pancreatitis requiring hospitalization, and the other responding patient developed significant, permanent cognitive decline without clear etiology.
8eea62084ca7e541d918e823422bd82e Conclusion
This study confirms PS as a strong predictor of OS in refractory NSCLC patients receiving ICIs. Overall, patients with PS 3 suffered poor outcomes with ICIs. However, 2 patients with PS 3 responded to ICI, and both were still alive over 1.5 years from the initial ICI dose. Still, ICI toxicity was common in this population. More experience with PS 2-3 patients should be reported to further evaluate the safety and efficacy of ICIs in this setting. Biomarker-driven selection with high tumor PD-L1 or tumor mutation burden may help improve appropriate utilization of ICIs in this challenging population.
6f8b794f3246b0c1e1780bb4d4d5dc53
