Virtual Library
Start Your Search
Alberto A. Chiappori
Author of
-
+
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
-
+
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 | Presenting Author(s): Alberto A. Chiappori
- 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
-
+
P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.09-17 - A Call to Action: Rapid Collection of Post-Mortem Lung Cancer Tissue in the Community to Enable Lung Cancer Research (ID 12584)
16:45 - 18:00 | Author(s): Alberto A. Chiappori
- Abstract
Background
Posthumous rapid tissue donation (RTD) provides an opportunity to understand treatment-resistant lung cancers with preservation of valuable tumor and non-tumor specimens from primary and metastatic sites.
a9ded1e5ce5d75814730bb4caaf49419 Method
Consent to participate in the lung RTD program was obtained during patient care. When death occurred, tumor and paired non-tumor, cytology, and blood specimens were preserved as formalin-fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin (H&E) staining and programmed death ligand-1 (PD-L1) immunohistochemistry. Massively parallel sequencing was performed on 11 specimens.
4c3880bb027f159e801041b1021e88e8 Result
To date, 21 patients consented to participate in the RTD program. Post-mortem specimens (N=180) were preserved from 9 patients and the other patients remain alive. Evaluation of H&E slides confirmed well-preserved tissue. PD-L1 immunohistochemistry revealed heterogeneous expression between tumor sites. Next generation sequencing provided high quality data on all 11 tested samples.
8eea62084ca7e541d918e823422bd82e Conclusion
Rapid donation of post-mortem tissue from lung cancer patients is feasible and provides high quality specimens for research. Post-mortem tissue collection of primary and metastatic tumors facilitates studies of tumor mutation evolution, mechanisms of drug resistance, and biomarker expression.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.13-10 - Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Erlotinib in pts with EGFRm NSCLC (ID 14272)
16:45 - 18:00 | Author(s): Alberto A. Chiappori
- Abstract
Background
Bemcentinib is a first-in-class, oral, selective AXL TKI which is being evaluated as a combination therapy across several phII clinical trials. Increased AXL expression is associated with innate immune suppression and the appearance of resistance to targeted therapies in models of NSCLC and pt samples. AXL inhibition via bemcentinib prevents the appearance of such resistance in vivo and has shown immunomodulatory effect in AML patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
This study was designed to confirm the safety and tolerability of bemcentinib as a monotherapy and when administered in combination with erlotinib (arm A). Pts with activating EGFR mutation driven NSCLC who had progressed on an approved EGFR inhibitor (arm B) or were receiving erlotinib in the first line setting (arm C) were treated with bemcentinib at RP2D in combination with full dose erlotinib to evaluate the potential of bemcentinib to reverse or prevent resistance to EGFR targeted therapy, respectively. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at C1D1 and C2D1.
4c3880bb027f159e801041b1021e88e8 Result
2 out of 8 pts (25%) with stage IV disease who received bemcentinib monotherapy achieved SD for close to 1 year including evidence of tumour shrinkage of 19% in 1 pt. 1 pt who had progressed on previous erlotinib monotherapy (12.5%) achieved a PR receiving bemcentinib in combination with erlotinib and remains on treatment well beyond 2 years later (arm A). A further 3 pts had SD at 6 wks. 11 patients (4 female, median age 58; 38-67) were enrolled in arm B and had received a median of 2 (1 - 4) previous lines of cytotoxic chemotherapy and a median of 2 previous EGFR inhibitors. 2 of these 11 pts (18%) including 1 pt who was refractory to erlotinib therapy at the onset of combination therapy remain on treatment more than 6 months into therapy at the time of writing with best responses of PR and SD, respectively. 1 further pt had SD at 6 weeks. The most common treatment-related AEs have been gastrointestinal and rash.There was no evidence of any impact of bemcentinib on erlotinib pharmacokinetics. Protein biomarkers predictive of pt benefit following bemcentinib treatment were identified.
8eea62084ca7e541d918e823422bd82e Conclusion
Bemcentinib can be safely administered in combination with erlotinib to pts with NSCLC and achieves additional benefit in a proportion of patients who do not have T790M and have progressed on EGFR inhibition or are maintained on erlotinib alone. Clinical trial information: NCT02424617.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.15-23 - Are there Ethnic Disparities in the Clinical Outcomes of Non-Small Cell Lung Cancer Hispanic Patients Treated with Immunotherapy? (ID 12359)
16:45 - 18:00 | Author(s): Alberto A. Chiappori
- Abstract
Background
Immunotherapy outcomes in non-small cell lung cancer (NSCLC) are widely available thanks to studies that got the approval of PD-1/PD-L1 inhibitors. However a careful review of ethnicity can find that most of the studies were done in Non-Hispanic White or Asian populations. There is little known about the outcomes in Hispanics (H). It is well known that Hispanics (H) in the US seem to have a lower age-adjusted mortality in NSCLC and have a different gene expression profile than NHW with higher prevalence of EGFR mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed clinical outcomes in 216 H pts with NSCLC stage IV treated with atezolizumab, nivolumab or pembrolizumab at 4 large cancer centers (Memorial Cancer Institute, University of Miami and Moffitt Cancer Center all of them in Florida (US), and the National Cancer Institute in Peru. These patients have failed at least one line of chemotherapy previously. All of these patients did not have actionable genes (EGFR. ALK, ROS-1). We assessed overall response rate ORR (CR+PR) as main objective and disease control rate (DCR: ORR+SD), median PFS (progression free survival) & overall survival (OS) and PFS at 6m and 12m as secondary objectives.
4c3880bb027f159e801041b1021e88e8 Result
Most of the pts were males: 116 (54%), 82% adenocarcinomas and the median age was 65 years (range: 37-88y). The ORR was 16% and the DCR that shows the clinical benefit was 67%. ORR and DCR were similar in adenocarcinomas (20%/68%) and squamous cell carcinomas (17%/64%). The progression free survival (PFS) at 6 months (m) and 12m were 80% and 56% respectively. Median PFS 14.5m and median overall survival were 19m, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
ORR for NSCLC pts treated with immunotherapy is 16% in Hispanics treated at 4 cancer centers compared to an expected 20% ORR for NHW as reported in the literature. Therefore it appears that Hispanics might not have a benefit from immunotherapy to the extent that NHWs do. We need a larger cohort and prospective studies to validate these findings.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
-
+
PL02.01 - Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC (ID 14701)
08:15 - 08:25 | Author(s): Alberto A. Chiappori
- Abstract
- Presentation
Background
In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint overall survival (OS) for PACIFIC.
Patients with WHO PS 0/1 (any PD-L1 tumor status) who received ≥2 cycles of platinum-based CRT were randomized (2:1) 1–42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS from randomization (blinded independent central review; RECIST v1.1) and OS (interim analysis reported). Secondary endpoints included time to death or distant metastasis (TTDM) and PFS2 (time to second progression) from randomization and safety. Time to first/second subsequent therapy or death (TFST/TSST) were supportive assessments for PFS/PFS2.
Between May 2014 and April 2016, 713 patients were randomized of whom 709 received treatment (durvalumab, n=473; placebo, n=236). As of March 22, 2018 (data cutoff), median follow-up duration was 25.2 months (range, 0.2–43.1). After discontinuation, 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469–0.997; P=0.00251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR), respectively. Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41–0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved the updated TTDM (stratified HR 0.53, 95% CI, 0.41–0.68), as well as PFS2 (stratified HR 0.58, 95% CI, 0.46–0.73), TFST (stratified HR 0.58, 95% CI, 0.47–0.72) and TSST (stratified HR 0.63, 95% CI, 0.50–0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs, and no new safety signals were identified.
Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.
a9ded1e5ce5d75814730bb4caaf49419Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
