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D. Morgensztern
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 2
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.06 - Viagenpumatucel-L Bolsters Response to Nivolumab Therapy in Advanced Lung Adenocarcinoma: Preliminary Data from the DURGA Trial (ID 4650)
14:56 - 15:02 | Author(s): D. Morgensztern
- Abstract
- Presentation
Background:
Viagenpumatucel-L (HS-110) is an allogeneic whole-cell vaccine, selected for high expression of adenocarcinoma tumor antigens, transfected to secrete gp96-Ig. Prior studies with HS-110 (and related gp96-Ig vaccines) have shown a correlation between increases in CD8+ tumor infiltrating lymphocytes (TIL) and tumor response. The DURGA trial was designed evaluate the combination of HS-110 and nivolumab, in an attempt to increase tumor inflammation and improve the response rates observed with nivolumab alone. Clinical Trial identifier: NCT02439450
Methods:
Patients with advanced lung adenocarcinoma who received at least one prior line of therapy were assigned to two cohorts based on baseline levels of TIL in patient biopsies: low TIL (≤10% CD8+ T cells) or high TIL (>10% CD8+ T cells). All patients received standard of care nivolumab 3 mg/kg every 2 weeks and weekly HS-110 for 18 weeks until intolerable adverse events, disease progression, or death. Each 9-patient Phase 1b cohort could be expanded to 30 patients in Phase 2 based on exhibited efficacy. The primary endpoint was safety and tolerability. Biopsies at baseline and Week 10 were used to track changes in TIL and PD-L1 staining. Peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry for detection of circulating leukocyte subsets. ELISPOT was used to track antigen-specific immune response.
Results:
HS-110 vaccine and nivolumab combination was well tolerated with a safety profile consistent with single-agent nivolumab. Among the 8 initial patients, only 4 had optimal biopsies which showed 2 patients with high and 2 with low TILs. PD-L1 was >1% in 3 patients. IFNγ ELISPOT assay defined 4 patients as immune responders (doubling of IFNγ-secreting cells after re-stimulation with total vaccine antigen and individual cancer antigens, IR) and 4 patients as non-immune responders (NIR). The overall response rate (ORR) was 50% in the IR patients and 0% in the NIR patients. At the time of the data cutoff, 6 patients remain alive, including the 4 IR patients, with ongoing responses for 150 to 326 days. Patients with objective response also exhibited injection site reactions and maculopapular rash consistent with HS-110 mechanism of action, decreased Myeloid Derived Suppressor Cells (MDSC) in the blood, and increased markers of activated CD8+ T cell subsets by flow cytometry (CD8+CTLA-4+, CD8+Tim3+). Although the pathology specimens were sub-optimal in the two responding patients, the limited tissue available showed lower baseline TILs in both patients.
Conclusion:
Allogeneic gp96-based vaccination may have synergistic activity in combination with immune checkpoint inhibitors.
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MA09.09 - First-In-Human Phase 1 Study of ABBV-399, an Antibody-Drug Conjugate (ADC) Targeting C-Met, in Patients with Non-Small Cell Lung Cancer (NSCLC) (ID 5008)
15:20 - 15:26 | Author(s): D. Morgensztern
- Abstract
- Presentation
Background:
The c-Met receptor is overexpressed in ~50% of patients with NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data support ABBV-399 as a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells.
Methods:
In a 3+3 dose-escalation design, ABBV-399 was administered at doses ranging from 0.15 to 3.3 mg/kg once every 21 days to patients with advanced metastatic solid tumors (NCT02099058). ABBV-399 was then studied in a dose-expansion cohort in 16 patients with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) NSCLC that had progressed on ≥2 prior lines of therapy. ABBV-399 was also studied in combination with erlotinib in 10 patients with NSCLC, 8 of whom were c-Met+. Overexpression of c-Met was assessed by an IHC assay utilizing the SP44 antibody (Ventana; Tucson, AZ, USA).
Results:
As of June 27, 2016, 48 patients with solid tumors received ≥1 dose of ABBV-399. The dose-limiting toxicity (DLT) for ABBV-399 was febrile neutropenia, which occurred in 2 patients (1 each at 3 and 3.3 mg/kg). There were no treatment-related deaths. Monotherapy treatment-related adverse events (AEs) occurring in ≥10% of patients (including all dose levels and all grades) were fatigue (25.0%), nausea (22.9%), neuropathy (14.6%), decreased appetite (12.5%), vomiting (12.5%), and hypoalbuminemia (10.4%). Based primarily on safety and tolerability, a 2.7-mg/kg dose was chosen for dose expansion in patients with c-Met+ advanced NSCLC. Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC patients had a confirmed partial response (PR) with duration of response (DOR) 3+, 3, and 4.5 months. At week 12, 6 of 16 patients treated (37.5%) had disease control. Ten patients received ABBV-399 in combination with erlotinib. No DLTs were observed and AEs related to ABBV-399 occurring in ≥2 patients were acneiform rash (40.0%), fatigue (30.0%), and dry skin (20.0%). Three of 8 (37.5%) evaluable ABBV-399 + erlotinib-treated c-Met+ patients had a confirmed PR with DOR 2+, 4+, and 5+ months. Two of the 3 patients with PR had EGFR-mutated tumor, and previous TKI- and platinum-based chemotherapy had failed.
Conclusion:
ABBV-399 is well tolerated at a dose of 2.7 mg/kg every 21 days and has demonstrated antitumor activity in patients with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated data of antitumor activity and safety of ABBV-399 as monotherapy and in combination with erlotinib in c-Met+ NSCLC patients will be presented.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-002 - Patterns of Chemotherapy Use and Overall Survival (OS) of Patients with Stage IV Squamous Lung Cancer (SCC) (ID 5216)
14:30 - 14:30 | Author(s): D. Morgensztern
- Abstract
Background:
Chemotherapy is standard of care for patients with metastatic SCC. There is limited information on the use and outcome of patients with metastatic SCC who receive chemotherapy. We used the National Cancer Data Base (NCDB) to investigate the use and survival of patients receiving chemotherapy for stage IV SCC.
Methods:
The NCDB was queried for patients≥ 18 years, diagnosed with stage IV SCC between 2004-2013 for whom chemotherapy data was available. The percentage of patients receiving chemotherapy within 2 months of diagnosis was calculated. Patients were stratified by age (<50, 50-70 and >70 years), Charlson-Deyo comorbidity score (0, 1 and 2), gender, and period of diagnosis (2004-2006, 2007-2009, 2010-2012) to evaluate patterns of chemotherapy use. Median, 1-year and 2-year OS were calculated for patients that received chemotherapy using Kaplan Meier method.
Results:
Among the 86,200 patients that met the eligibility criteria, 40,147 (46.6%) patients received chemotherapy, which included single agent (n=3,912; 9.7%) multiagent (n=32,737;81.5%) and number of agents unknown (n=3,498;8.7%). A total of 46,053 (53.43%) patients did not receive chemotherapy due to chemotherapy not recommended (n=5,397; 11.7%), patient refusal (n=6,119; 13.3%) and other/unknown reasons (n=34,537; 75%). Patients receiving multi-agent chemotherapy were younger than those receiving single agent chemotherapy (65.6 vs 71.5 years). Chemotherapy use declined with increase in comorbidity score (50.4% for score of 0, 44% for score of 1 and 36.2% for score of 2). The median, 1-year and 2-year OS for patients receiving chemotherapy were 7.5 months, 30.6% and 11.8% respectively (Table).OS for patients receiving chemotherapy by risk factor
Risk factor Median survival (months) 1 year OS 2 year OS Age <50 7.6 29.7% 11.5% 50-70 7.8 32.0% 12.4% >70 7.0 28.5% 10.8% Gender Male 7.3 29.0% 10.7% Female 7.9 33.7% 13.8% Year of diagnosis 2004-2006 7.3 28.8% 10.7% 2007-2009 7.5 31.0% 11.8% 2010-2013 7.7 31.6% 12.7% Charlson-Deyo comorbidity score 0 8.0 32.6% 12.7% 1 7.1 28.4% 10.6% 2 6.3 24.9% 9.2% All patients 7.5 30.6% 11.8%
Conclusion:
Most patients with metastatic SCC do not receive chemotherapy. The OS for patients with metastatic SCC remains poor, especially in patients over the age of 70, in men and those with multiple comorbidities.
